CN101578043A - Antimicrobial polymeric articles, processes to prepare them and methods of their use - Google Patents

Antimicrobial polymeric articles, processes to prepare them and methods of their use Download PDF

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Publication number
CN101578043A
CN101578043A CNA2007800489779A CN200780048977A CN101578043A CN 101578043 A CN101578043 A CN 101578043A CN A2007800489779 A CNA2007800489779 A CN A2007800489779A CN 200780048977 A CN200780048977 A CN 200780048977A CN 101578043 A CN101578043 A CN 101578043A
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articles
mixture
silver
eyeglass
particulate
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CN101578043B (en
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S·马哈德文
A·哈诺尔卡
O·拉索尔
李永成
C·W·沃克
T·R·鲁尼
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Johnson and Johnson Vision Care Inc
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Johnson and Johnson Vision Care Inc
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
    • A61L12/088—Heavy metals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/42—Block-or graft-polymers containing polysiloxane sequences
    • C08G77/442—Block-or graft-polymers containing polysiloxane sequences containing vinyl polymer sequences
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
    • C08L83/04—Polysiloxanes
    • C08L83/06—Polysiloxanes containing silicon bound to oxygen-containing groups
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
    • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
    • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
    • G02B1/041—Lenses
    • G02B1/043—Contact lenses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/624—Nanocapsules
    • C—CHEMISTRY; METALLURGY
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    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/04—Polysiloxanes
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    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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Abstract

the invention relates to antimicrobial polymeric articles containing metal salt particles having a particle size of less than about 200 nm dispersed throughout the polymer and methods for their production.

Description

Antimicrobial polymeric articles, its preparation process and using method thereof
Invention field
The present invention relates to antimicrobial polymeric articles and its production and use.
Background of invention
Material with antimicrobial characteristics has been used to multiple application.In medical treatment device such as conduit, prosthese, implant, Ophthalmoligic instrument, the surface microorganism invasion and attack can cause severe infections and apparatus function obstacle.The biofouling with material of spreading that also causes food spoilage, food borne transmission disease is infected on surface-center.Therefore, the development antimicrobial material is used for health care and bio-medical instrument, food and personal hygiene industry are extremely important.
In dentistry, Wound healing and bone regeneration and medical treatment device, silver salt is used for the human health care as postoperative bactericide and medical treatment has had very long history.Silver nitrate has been used to prevent neonatal ophthalmia neomatorum.The 1800's were introduced collargol, and the standby as medical silver nitrate before generation nineteen thirty is extensive use of.
Silver compound is added in the medical treatment device with various forms recently, as solubility and insoluble salt, the complex compound, argent and the silver oxide that combine with polymer and zeolite.But when many these silver compounds mixed in the polymer composition, multiple shortcoming appearred in polymer composition, comprised the high muddy degree, carried that silver is inconsistent, production process is complicated, discharge silver too quickly or lack effect.
Open already silver had been mixed several technology in the polymer substrate, comprise chemical operation as reduction or synthetic complexing silver compound, make preformed silver-colored particulate and mixed with polymers, perhaps Fu Za physical technique such as sputter and plasma-deposited.These process complexity are not necessarily as one man inserted silver compound in the polymeric material.The open already technology that microkinetic slaine such as silver salt are mixed medical treatment device as colloidal metal salt particulate.But, described salt mixed the method in the device that forms by light polymerization and method that described salt is mixed in the active mixture that contains reductant is announced as yet.
Contact lenses have been used to improve eyesight on market since generation nineteen fifty.First kind of contact lenses prepares with hard material.The patient wears when waking up, and takes off and cleans.This field has produced soft contact lens at present, and this contact lenses can be worn several days or the longer time continuously, did not need to take off cleaning.Though many patients like these eyeglasses, because its comfort level increases, these eyeglasses can produce bad reaction to the user.Excessively use this eyeglass help bacterium or other microorganism particularly pseudomonas aeruginosa (Pseudomonas aeruginosa) accumulate in the soft contact lens surface.The gathering of bacterium and other microorganism can cause bad reaction such as the acute blood-shoot-eye illness of contact lenses etc.Though the problem of bacterium and other microorganism is most commonly in excessive use soft contact lens, the gathering of bacterium and other microorganism also sees the hard contact lens wearer.
Therefore, still need to prepare Ophthalmoligic instrument, as suppressing bacterium or other growth of microorganism and/or bacterium or other microorganism adhering at the lip-deep contact lenses of Ophthalmoligic instrument.And need the preparation Ophthalmoligic instrument, as not impelling bacterium or other microorganism adhering and/or being grown in contact lenses on the contact lens surface.Also need to prepare the contact lenses of the inhibition bad reaction relevant with bacterium or other growth of microorganism.
The accompanying drawing summary
Fig. 1 show in embodiment 16 and comparing embodiment 2 eyeglasses silver concentration as with the figure of lens edge distance function.
Fig. 2 is the release of silver in the contact lenses of embodiment 16 and comparing embodiment 2 preparations, as the comparison diagram of the function of time.
Fig. 3 is that the effect of contact lenses resisting pseudomonas aeruginosa (Pseudomonas aeruginosa) of embodiment 16 and comparing embodiment 2 preparations is as the comparison diagram of the function of time.
Fig. 4 shows the UV-VIS spectrum of embodiment 22 and synthetic embodiment 3 mixtures.
Fig. 5 shows the UV-VIS spectrum of the active mixture of embodiment 23A-B.
Summary of the invention
In one embodiment, the present invention relates to the articles for use that form by at least a polymer, described polymer comprises the antimicrobial metal salt particulate of comprehensive equally distributed granularity less than about 200nm, wherein said articles for use make pseudomonas aeruginosa (Pseudomonas aeruginosa) and at least a demonstration of staphylococcus aureus (s aureus) at least about the minimizing of 0.5log, compare about 70 micron thickness turbidity values less than about 100% with the CSI eyeglass.
In another embodiment, the present invention relates to comprise the process of following steps:
(a) make at least a salt precursor, optional with at least a living polymer component of mixture, be dissolved in the solvent to form the salt precursor mixture;
(b) make at least a metal agent and at least a dispersant, optional with at least a active component, be dissolved in and form dispersant-metal agent complex compound in the solvent, to form the metal agent mixture, wherein said solvent and component can be identical or different;
(c) described salt precursor mixture and described metal agent mixture are mixed with formation under the particulate formation condition and contain at least a antimicrobial metal salt [M Q+] a[X Z-] bContain particle mixture;
(d) make other active component and described containing optional mixing of particle mixture contain the particulate active mixture with formation; Prerequisite is not comprise active component when step (a) with (b), and (d) adds at least a active component in step; With
Make describedly to contain particulate active mixture reaction forming antimicrobial polymeric articles, what described reaction condition was enough to make described metal agent that step (c) adds remains M at least about 90%M in described polymeric articles Q+
In also having another embodiment, the present invention relates to a kind of process, this process comprises with the light of the above wavelength of correction critical wavelength of described slaine particulate, heat or its combination and solidification active mixture and contains the articles for use of antimicrobial metal salt particulate with formation that described active mixture contains stable granularity and is antimicrobial metal salt particulate and at least a free radical activity component below about 200nm or the 200nm.
Detailed Description Of The Invention
The present invention includes a kind of antimicrobial articles for use, described antimicrobial articles for use make at least a of pseudomonas aeruginosa (Pseudomonas aeruginosa), staphylococcus aureus (Staphyloccus aureus) or both show minimizing at least about 0.5log, turbidity value is less than about 100%, comprise following, form or form by following substantially by following: granularity is less than the antimicrobial metal salt particulate of about 200nm, and described particulate is dispersed at least a polymer of forming described articles for use.In some embodiments, granularity is less than about 100nm, in other embodiments less than about 50nm.The granularity of antimicrobial metal salt particulate in the available scanning electron microscopy measurement articles for use.
When being used for this paper, the articles for use that term " antimicrobial " refers to have following one or more characteristics: suppress bacterium or other microorganism adhering in articles for use, suppress bacterium or other microorganism and on articles for use, grow, kill bacterium or other microorganism of articles for use surface or articles for use peripheral region.Be used for when of the present invention, bacterium or other microorganism adhering appear in growth on the articles for use and bacterium or other microorganism in articles for use, bacterium or other microorganism and are generically and collectively referred to as " microorganism troops " on the articles for use surface.Preferred articles for use of the present invention make bacterium alive or the demonstration of other microorganism at least about the minimizing of 0.25log, show the minimizing at least about 0.5log in some embodiments, show the minimizing (〉=90% suppresses) at least about 1.0log in some embodiments.This bacterioid or other microorganism include but not limited to pseudomonas aeruginosa (Pseudomonas aeruginosa), Acanthamoeba (Acanthamoeba species), staphylococcus aureus (Staphyloccus.aureus), Escherichia coli (E.coli), Staphylococcus epidermidis (Staphyloccus epidermidis) and serratia marcesens (Serratia marcesens).
The free radical activity component comprises can be by the polymerizable components of radical initiation reaction polymerization.The limiting examples of free radical activity group comprises (methyl) acrylate, styryl, vinyl, vinethene, C 1-6Alkyl (methyl) acrylate, (methyl) acrylamide, C 1-6Alkyl (methyl) acrylamide, N-vinyl lactam, N-vinylamide, C 2-12Alkenyl, C 2-12Alkenyl phenyl, C 2-12Alkenyl naphthyl, C 2-6Alkenyl phenyl C 1-6Alkyl, O-vinyl carbamate and O-vinyl carbonic ester.
When being used for this paper, term " slaine " refers to have general formula [M Q+] a[X Z-] bAny molecule, wherein X comprises any negatively charged ions, a, b, q and z independently be 〉=1 integer, q (a)=z (b).M can be any positive charge metal ion, is selected from but is not limited to following Al + 3, Cr + 2, Cr + 3, Cd + 1, Cd + 2, Co + 2, Co + 3, Ca + 2, Mg + 2, Ni + 2, Ti + 2, Ti + 3, Ti + 4, V + 2, V + 3, V + 5, Sr + 2, Fe + 2, Fe + 3, Au + 2, Au + 3, Au + 1, Ag + 2, Ag + 1, Pd + 2, Pd + 4, Pt + 2, Pt + 4, Cu + 1, Cu + 2, Mn + 2, Mn + 3, Mn + 4, Zn + 2, Se + 4, Se + 2And composition thereof.In another embodiment, M can be selected from Al + 3, Co + 2, Co + 3, Ca + 2, Mg + 2, Ni + 2, Ti + 2, Ti + 3, Ti + 4, V + 2, V + 3, V + 5, Sr + 2, Fe + 2, Fe + 3, Au + 2, Au + 3, Au + 1, Ag + 2, Ag + 1, Pd + 2, Pd + 4, pt + 2, pt + 4, Cu + 1, Cu + 2, Mn + 2, Mn + 3, Mn + 4, Se + 4And Zn + 2And composition thereof.The example of X includes but not limited to CO 3 -2, NO 3 -1, PO 4 -3, Cl -1, I -1, Br -1, S -2, O -2, acetate and composition thereof etc.Other X comprises negatively charged ions, and this negatively charged ions comprises CO 3 -2, SO 4 -2, PO 4 -3, Cl -1, I -1, Br -1, S -2, O -2, acetate etc., as C 1-5Alkyl CO 2 -1In another embodiment, X can comprise CO 3 -2, SO 4 -2, Cl -1, I -1, Br -1, acetate and composition thereof.When being used for this paper, the term slaine does not comprise zeolite, as is disclosed in the zeolite of US-2003-0043341-A1.In one embodiment, a is 1,2 or 3.In one embodiment, b is 1,2 or 3.In one embodiment, metal ion is selected from Mg + 2, Zn + 2, Cu + 1, Cu + 2, Au + 2, Au + 3, Au + 1, Pd + 2, Pd + 4, Pt + 2, Pt + 4, Ag + 2And Ag + 1And composition thereof.Special preferable alloy ion is Ag + 1The example of suitable metal salt includes but not limited to manganese sulfide, zinc oxide, zinc carbonate, calcium sulphate, selenium sulfide, cupric iodide, copper sulfide and cupric phosphate.The example of silver salt includes but not limited to silver carbonate, silver orthophosphate, silver sulfide, silver chlorate, silver bromide, silver iodide and silver oxide.In one embodiment, slaine comprises at least a silver salt such as silver iodide, silver chlorate and silver bromide.
At least about 90%, adopt slaine [M at least about 95% metal M in some embodiments in some embodiments of the present invention Q+] a[X Z-] bForm.Available ionic metal and metal 0Measured value calculate percentage.For example, when articles for use are hydrogel contact lens, when antimicrobial metal salt is silver iodide, the available method that is described in USP AppVII extract phosphate buffered salt solution (Dulbecco ' s phosphate buffered saline (PBS) 10 *, available from MediaTech, Inc.Herndon, Va) eyeglass in no longer includes salt in extracting solution, calculates ionic metal.After the extraction, measure articles for use with instrumental neutron activation analysis (" INAA ").When under used condition, extracting Ag 0The time, the whole silver that extract in the eyeglass of measuring the back all are Ag 0Oxidation state.
For articles for use wherein are the medical treatment devices that contact with water miscibility body fluid such as blood, urine, tear or saliva, and when needing antimicrobial efficacy greater than about 12 hours, the K of slaine in 25 ℃ of pure water SpLess than about 2 * 10 -10In one embodiment, the solubility product constant of slaine is no more than about 2.0 * 10 -17Mole/L.In certain embodiments, articles for use can be biologic medical equipment, Ophthalmoligic instrument or contact lenses.
When being used for this paper, term " pure " refers to the quality of institute's water, as is defined in CRC Handbookof Chemistry and Physics, the 74th ThVersion, CRC Press, Boca Raton Florida, 1993.Measure the solubility product constant (K of various salt at 25 ℃ of pure water Sp) be disclosed in CRCHandbook of Chemistry and Physics, the 74th ThVersion, CRC Press, Boca RatonFlorida, 1993.For example, if slaine is silver carbonate (Ag 2CO 3), K then SpBe expressed from the next
Ag 2CO 3(s)→2Ag +(aq)+CO 3 2-(aq)
Following calculating K Sp
K sp＝[Ag +] 2[CO 3 2]
When silver carbonate dissolved, per 2 silver-colored cations just had 1 carbonate anion, [CO in the solution 3 2-]=1/2[Ag +], the solubility product constant formula can rearrange the silver concentration that obtains dissolving, and is as follows
K sp＝[Ag +] 2(1/2[Ag +])＝1/2[Ag +] 3
[Ag +]＝(2K sp) 1/3
Found that the solubility product constant that contains 25 ℃ of measurements is no more than about 2 * 10 -10The articles for use of slaine will continue to discharge metal 1 day to 30 days or more of a specified duration in the eyeglass.In one embodiment, suitable slaine comprises silver iodide, silver chlorate, silver bromide and composition thereof.In another embodiment, slaine comprises silver iodide.
Articles for use polymer manufacture of the present invention can be used for packing, tank and wrappage, comprises the packing of food, medicine and medical supplies, biologic medical equipment etc.Biologic medical equipment comprises conduit, support, storage blood bag and pipe, prosthese, implant and Ophthalmoligic instrument, comprises lens (hereinafter describing these eyeglasses in detail).In one embodiment, articles for use of the present invention are with the preparation of light polymer, polymer, particularly with the preparation of free radical activity component, as by being exposed to visible photopolymerisable component.In other embodiments, articles for use are exposed to visible light and ultraviolet light in use.These type of articles for use comprise packing, tank, plastic wraps and Ophthalmoligic instrument.In one embodiment, articles for use of the present invention are Ophthalmoligic instruments.
These articles for use known in the art, available multiple polymers forms.In some embodiments, articles for use can form with a kind of polymer, with different polymer coatings.Can make anti-microbial polymer form a device or a device part, perhaps use making coatings.
In many these embodiments, the transparency person of being to use of articles for use is concerned about.For example, in a non-limiting embodiments, when articles for use are Ophthalmoligic instrument such as contact lenses, are used for slaine of the present invention and are particularly suitable for very little granularity.In some embodiments, the present invention realizes granularity less than about 200nm, less than about 100nm, in some embodiments less than about 50nm.This very little granularity less than visible wavelength makes articles for use of the present invention needing be particularly suitable for transparent purposes.This type of embodiment includes but not limited to contact lenses, intraocular lens (intraocular lenses), storage blood bag and pipe and food Package.When not requiring the optical quality of polymer, can use particulate greater than above scope.
In one embodiment, the slaine particulate also is evenly distributed at least a polymer of forming articles for use." evenly distribute " and be used for the aggregation that this paper refers to not form particulate, not obvious certain part that contains antimicrobial metal salt polymer that concentrates on of particulate.In one embodiment, evenly distribute and refer in the polymer that the difference of slaine particle concentration (based on dry product weight meter, being measured as weight %) is less than about 20% between the zone, any two place.In another embodiment, the difference of slaine particle concentration is less than about 10% between the zone, any two place, and in also having other embodiment, the difference in zone, any two place of polymer is less than about 5%.The available element analytical technology is measured the uniformity that distributes in the finished product, induces emission characteristic x line with high energy electron.Electron probe microanalysis (EPM) (Cameca SX100 and SX50 autoelectrinic microprobe have 4 kinds of wavelength spectrometers, with the analysis condition of 20Kev, 50nA and 20um) is used in this application.
In one embodiment, articles for use of the present invention had not both had the vision muddiness not have unfavorable color yet.Compare by using with the CSI eyeglass of hereinafter describing in detail, the turbidity % of the sample in measurement that thickness is about 70 microns measures the transparency of antimicrobial articles for use.Can be easy to obtain less than turbidity value about 100%, with the present invention less than about 50%.
The color of the final polymeric articles of available spectrophotometer measurement is expressed as CIE 1976L *a *b *Grade.The L of articles for use of the present invention *Can be greater than about 89, in some embodiments greater than about 90, a *Less than about 2, in some embodiments less than about 1.4.Should carry out color measuring to the polymer that does not contain the polymers compositions (as UV absorbent, processing coloring agent (handling tint), photochromic compound etc.) that may influence finished color.
Measure the amount of slaine in polymer based on the dry polymeric gross weight.The amount of slaine in polymer depends on the final use and the final instructions for use of articles for use.For example, in one embodiment, when articles for use were contact lenses, transparency and color were very crucial.Articles for use are that contact lenses and slaine are in the embodiment of AgI therein, and based on the polymer dry restatement, the amount of silver in polymer is extremely about 1000ppm of about 100ppm, is that 200ppm is to about 1000ppm in some embodiments.For other embodiment, based on the polymer dry restatement, the amount of silver in polymer can be about 0.00001 percetage by weight (0.1ppm) to about 10.0 percetages by weight, and preferred about 0.0001 (1ppm) is to about 1.0 percetages by weight, and most preferably from about 0.0001 (1ppm) is to about 0.1 percetage by weight.Aspect the adding slaine, the molecular weight decision metal ion of slaine is converted into the percetage by weight of slaine, and those skilled in the art can be provided by the salt amount that provides the aequum antimicrobial metal essential.
In one embodiment, articles for use of the present invention can form through the following steps
(a) at least a salt precursor is dissolved at least a living polymer component of mixture to form the salt precursor mixture;
(b) at least a metal agent and at least a dispersant are dissolved in and form metal agent-dispersant complex compound at least a living polymer component of mixture, to form the metal agent mixture;
(c) described salt precursor mixture is mixed with formation with described metal agent mixture under the particulate formation condition and contain the particulate active mixture;
(d) make other active polymer composition contain with described that the particulate active mixture is optional to be mixed; With
(e) make described antimicrobial polymeric articles or the part that contains the reaction of particulate active mixture with the formation metalline, wherein exist with metallic salt form at least about 90% antimicrobial metal M.
The term slaine has above-mentioned implication.Term " salt precursor " refers to comprise the cationic any compound or the composition (comprising the aqueous solution) that can be replaced by metal ion.In the present embodiment, the preferred salt precursor is dissolved in the eyeglass preparation with about 1 μ g/mL or bigger concentration.This term does not comprise zeolite or activation silver, as be described in the zeolite of US2003/0043341 title, as be described in the activation silver of WO02/062402 title for " Antimicrobial Contact LensesContaining Activated Silver and Methods for Their Production (containing antimicrobial contact lenses of activation silver and preparation method thereof) " for " AntimicrobialContact Lenses and Methods of Use (antimicrobial contact lenses and using method) ".Compare with the antimicrobial metal amount that needs in the final plastic articles, the salt precursor that adds in the active mixture is at least stoichiometric amount, is molar excess in some embodiments.For example, 20 μ g AgI are present in the embodiment in the articles for use as slaine therein, and the amount of NaI in active mixture is at least about 12 μ g.The example of salt precursor includes but not limited to inorganic molecule such as sodium chloride, sodium iodide, sodium bromide, lithium chloride, lithium sulfide, vulcanized sodium, potassium sulfide, the sour sodium of tetrachloro silver, its mixture etc.The example of organic molecule includes but not limited to tetraalkyl ammonium lactate, tetraalkyl ammonium sulfate, tetraalkyl Yi Suan Phosphonium, tetraalkyl Liu Suan Phosphonium, quaternary ammonium halide Huo Phosphonium halide, as tetra-alkyl ammonium chloride, Si Wan Ji Phosphonium chloride, bromide, iodide etc.In one embodiment, precursor salt comprises sodium iodide.
Term " metal agent " refers to comprise any composition (comprising the aqueous solution) of metal ion.The example of this based composition includes but not limited to the aqueous solution or the organic solution of silver nitrate, silver trifluoromethanesulfonate, silver acetate, silver tetrafluoroborate, copper nitrate, copper sulphate, magnesium sulfate, zinc sulphate, its mixture etc.Can calculate the suitable concn of metal agent in solution based on the aequum that will be included in the slaine in the finished product.For example, in some embodiments, select metal agent concentration in case with about 0.00001 percetage by weight (0.1ppm) to about 10.0 percetages by weight, about 0.0001 (1ppm) is to about 1.0 percetages by weight, and about in another embodiment 0.0001 (1ppm) extremely about 0.1 percetage by weight slaine is provided in the finished product.
In some embodiments, preferred stable color.For example, when plastic articles was Ophthalmoligic instrument, preferred embodiment had color identical with active mixture and transparency.Known silver salt is a light sensitivity.Therefore, if careless when forming and solidify the articles for use that contain silver salt, then in articles for use, do not produce required silver salt.For example, silver iodide are light sensitivity to wavelength less than the light of about 400nm, if careless, then the active mixture by light-initiated curing may form bad yellow or brown eyeglass, and the prompting silver salt is reduced.By (" reactant mixture of the photocuring metalline of critical wavelength "), it is minimum that photoreduction is dropped to greater than the wavelength suitable with selected slaine bond energy with wavelength.For example, the bond energy of AgI is 60kcal/mol.Available electromagnetism formula calculates the wavelength relevant with this bond energy:
E AgI＝hc/(λN A)
Wherein h is a Plank ' s constant, and c is the light velocity, and λ is the incident radiation wavelength, N AIt is Avagadro ' s number.
For AgI, λ is 477nm.Consider that mold materials and packaging material and solution absorb or reflected energy the recoverable critical wavelength.Therefore for example, when articles for use are when containing the contact lenses of AgI, the direct molding preparation of plastics mould of these contact lenses energy loss 10% when propagating, proofread and correct critical wavelength and be:
λ＝(1-10％)×477nm
λ＝429nm
Therefore the condition of cure of the present embodiment comprises that wavelength is greater than about 429nm.Perhaps, available condition (such as but not limited to heat cure) the curing reaction mixture that does not comprise light.
Also can use the salt precursor of comparing molar excess with metal agent so that all metal agents all are converted into slaine basically, it is minimum that photoreduction is dropped to.Can accept about 1.1: 1 or bigger salt precursor: the metal agent mol ratio.This guarantees to adopt metallic salt form at least about 90% antimicrobial metal M in the finished product.In some embodiments, solidify articles for use with initator except that ultraviolet light and condition.
Metal agent mixture and salt precursor mixture be at least a also to comprise at least a dispersant, and in one embodiment, the metal agent mixture also comprises at least a dispersant.Suitable dispersant comprises the polymer that contains lone pair electrons functional group.The example of dispersant comprises the hydroxyalkyl methyl cellulose polymer, polyvinyl alcohol, polyvinylpyrrolidone, PEO, polysaccharide is (as starch, pectin, gelatin), polyacrylamide (comprising polydimethylacrylamiin), polyacrylic acid, organoalkoxysilane is (as 3-aminopropyltriethoxywerene werene (APS), methyl-triethoxysilane (MTS), phenyl-trimethoxy silane (PTS), vinyl-triethoxysilane (VTS) and 3-glycidoxypropyltrimewasxysilane (GPS)), polyethers is (as polyethylene glycol, polypropylene glycol), the borate of glycerine (BAGE), molecular weight is greater than about 10,000 and comprise the group that increases viscosity such as silicone macromonomer of hydrogen bond group (such as but not limited to hydroxyl and urethane groups) and composition thereof.
In one embodiment, dispersant is selected from borate (BAGE), gelatin and polyacrylic acid of hydroxyalkyl methyl cellulose polymer, polyvinyl alcohol, polyvinylpyrrolidone, PEO, glycerine, glycerine and composition thereof.In another embodiment, dispersant is selected from hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, PEO, gelatin, glycerine and BAGE and composition thereof.In also having another embodiment, dispersant is selected from polyvinyl alcohol, polyvinylpyrrolidone and PEO and composition thereof.
When dispersant is polymer, can have various molecular weights.Can use about 1000 to millions of molecular weight.The upper limit only is subjected to the restriction of dispersant solvability in metal salt mixture, salt precursor mixture and active mixture.For glucosides polymer such as gelatin and methylcellulose, molecular weight can surpass 100 ten thousand.For non-glucosides polymer such as polyvinyl alcohol, polyvinylpyrrolidone and polyacrylic acid, molecular weight can be about 2,500 to about 2,000,000, in some embodiments is about 10,000 to about 1,800,000 dalton, in other embodiment is about 20,000 to about 1,500,000 dalton.In some embodiments, can use, because the dispersant of this scope provides better static stabilization in some polymer systems greater than about 50,000 daltonian molecular weight.
Perhaps, also can measure according to kinematic viscosity, molecular weight with K value representation stably dispersing polymer, described mensuration is as being described in Encyclopedia of Polymer Science andEngineering, N-vinyl Amide Polymers (polymer science and engineering pandect, N-vinyl amide polymer), the 2nd edition, 17 volumes, 198-257 page or leaf, John Wiley ﹠amp; Sons Inc.When expressing by this way, the K value of non-glucosides polymer dispersant can be about 5 to about 150, is about 5 to about 100, about 5 to about 70 in some embodiments, is about 5 to about 50 in other embodiment.
When directly forming the slaine nanoparticle in the polymer active mixture, based on the weight % meter of all components in the active mixture, the amount of dispersant can be about 0.001% to about 40% weight.In some embodiments, the amount of dispersant can be about 0.01% weight to about 30% weight, is that about 0.1% weight is to about 30% weight in other embodiment.In some embodiments, dispersant also is the active component that is used to form polymeric articles, when containing the contact lenses of polyvinyl alcohol as preparation.In these embodiments, based on the weight % meter of all components in the active mixture, the usage amount of dispersant can be up to about 90% weight, in about at the most 100% weight of some embodiments.
In some embodiments, dispersant provides other advantage of resulting polymers.For example, when PVP was particle stabilizers, PVP can improve wettability, coefficient of friction, water content, the demoulding etc. except stabilising dispersions.In these embodiments, may need or preferably comprise than the required more dispersant of stabilising dispersions.In these embodiments, with other processing conditions of preferred balance as the degassing and maturation stage to guarantee to form the particulate of required size.
Salt precursor mixture and metal agent mixture are mixed under the particulate formation condition.When being used for this paper, the particulate formation condition comprises time, temperature and the pH that is adapted at active mixture and disperses to form the slaine particulate everywhere, the particle mean size of described particulate is less than about 200nm, in some embodiments less than about 100nm, in other embodiment less than about 50nm.
Mixing temperature can change along with the active component in the active mixture.Usually can use the active mixture freezing point to about 100 ℃ mixing temperature.In some embodiments, can use about 10 ℃ to about 90 ℃ mixing temperature, use in other embodiments about 10 ℃ to about 50 ℃ mixing temperature.
Can with before active mixture mixes with salt precursor mixture or metal agent mixture or both's degassing.
In one embodiment, salt precursor mixture or metal agent mixture can be introduced as one-jet by stream, perhaps can both be introduced simultaneously by dual-jet.In the one-jet method, solution such as metal agent mixture are entered in the agitating solution of saliferous precursor mixture and dispersant by injection with the speed of controlling.Perhaps, available dual-jet method adds metal agent mixture and salt precursor mixture in the agitating solution that contains dispersant simultaneously by two strands of independent jets.In some embodiments, may need to add dispersant, salt precursor mixture and/or the metal agent mixture of additional amount.
Availablely salt precursor mixture and metal agent mixture are added in the active mixture less than about 10 minutes time, in some embodiments, the interpolation time is about 10 seconds to about 5 minutes.
Can use any incorporation time,, and form stable dispersion as long as gained solution is uniformly.When being used for this paper, stable dispersion was at least about not sedimentation substantially in 12 hours.Commercial preferred incorporation time can comprise about 1 minute to several days, is about 10 minutes to about 12 hours in some embodiments.
Low MW polymer can use the high shear mixing technology, allows in the above lower bound time mixing of listed scope.
Also can or use under vacuum with active mixture in all nonreactive gas of any component make the active mixture degassing.Suitable inert gas comprises nitrogen, argon gas, comprises the mixture of nitrogen and argon gas etc.The pressure (as 10mbar) of available perfect vacuum at the most of outgasing proceeds to many about 60 minutes, proceeds to many about 40 minutes in some embodiments.The degassing step duration and the temperature and pressure that will use the specified activity mixture also depend on for example other factorses such as volatility of solvent for use.
This process makes the particulate maturation stage before also can being included in degassing step.Easier dissolving after very little particulate heats than big particulate.Therefore, when (as in Ophthalmoligic instrument), may need to comprise the particulate maturation stage in transparency very important use, enough big to guarantee particulate, not overcure when further processing (as sterilization, melt-processed, annealing, sintering) or storage.In the particulate maturation stage, with active mixture be heated to about 30 to about 70 ℃ temperature 5 minutes to 1 hour to reduce fines (fines).This step can be particularly conducive to the medical treatment device of sterilization.For example, when plastic articles was eyeglass, eyeglass must be avoided the vision muddiness when forming, and must keep avoiding the vision muddiness when processing (comprising packaging sterilizing), storage and use.Also can reduce the generation of fines by the amount that reduces dispersant.
In one embodiment, the granularity of at least 90% particulate is less than about 100nm in the active mixture, in another embodiment, the granularity of at least 90% particulate is less than about 80nm in the active mixture, in also having another embodiment, the granularity of at least 90% particulate is less than about 60nm in the active mixture.Can measure the granularity of particulate in the active mixture by light scattering (laser or dynamic), as the description of following Test Methods section.
The active mixture that the present invention contains particulate had not both had the vision muddiness not have bad color yet.Available white background subjectivity contrasts or uses L described below *a *b *Method is assessed the shortage of bad color.
Can choose other component of adding wantonly at blend step.Other polymers compositions comprises activated monomer, prepolymer and macromonomer, initator, crosslinking agent, chain-transferring agent, UV absorbent, wetting agent, release auxiliary agent, photochromic compound, nutrition and medicinal compound, colouring agent, dyestuff, pigment combinations etc.They can adopt any form to add, and comprise as monomer, oligomer or prepolymer.
If any component of active mixture can react the forming element metal with metal agent and this metal element is disadvantageous, then in one embodiment, after forming the slaine particulate but with before forming polymeric articles this component is added in active mixture at the curing activity mixture.For example, found AgNO 3Can form disadvantageous Ag with N,N-DMAA (DMA) reaction 0Therefore for the active mixture that contains DMA, in an embodiment (wherein slaine is AgI), afterwards DMA is added in the active mixture forming slaine particulate (AgI).Those skilled in the art are by making component and mix in solvent with metal agent and use the chemical analysis analysis, and perhaps the change by mixture naked eyes outward appearance can be easy to determine whether component brings into play the effect of reductant sometimes.
Perhaps can form nanoparticle slaine and polymer active mixture separately.For example, stable slaine particulate can followingly form: form the salt precursor solution that contains at least a salt precursor;
Form metal agent solution, this solution comprises about 20 at least a dispersant (weight average molecular weight is at least about 1000) and at least a metal agents to about 50% weight;
A kind of solution is added in the another kind of solution, and the speed of interpolation is enough to keep settled solution in the interpolation process, forms to contain the product solution of granularity less than the stable metal salt particulate of about 200nm; Dry described stable slaine particulate.Stable slaine particulate is the slaine particulate of granularity less than about 200nm, this particulate and at least a dispersant complexing.In some embodiments, the granularity of stable slaine particulate is less than about 100nm, in some embodiments less than about 50nm.
In the present embodiment, metal agent and salt precursor solution with (a) can the dissolution of metals agent, salt precursor and dispersant, (b) be not reduced to metal agent metal and (c) can be easy to form with any solvent that known method is removed.Can make water, alcohol or its mixture.Can select can the dissolution of metals agent and the suitable alcohol of salt precursor.When with silver nitrate and sodium iodide during as metal agent and salt precursor, can use alcohol as tert-pentyl alcohol, tripropylene glycol monomethyl ether and composition thereof and with the mixture of water.Also water separately.
Can use above-described any dispersant.Can use mixture.Dispersant can be included in metal agent or the salt precursor solution or the both comprises, perhaps can be included in the third solution, in it, add metal agent and salt precursor solution.In one embodiment, metal agent solution also comprises at least a dispersant.Salt precursor solution and metal agent solution all comprise in the embodiment of at least a dispersant therein, and dispersant can be identical or different.
The dispersion dosage that comprises is enough to provide the slaine granularity less than about 500nm (" particle size stable effective dose ").In the very important embodiment of finished product transparency, granularity is less than about 200nm, in some embodiments less than about 100nm, in other embodiments also less than about 50nm therein.In one embodiment, use at least about 20% weight fraction powder, to guarantee to obtain desired particle size at least a solution.In some embodiments, the mol ratio of dispersant unit and metal agent is at least about 1.5, at least about 2, in some embodiments at least about 4.When being used for this paper, dispersant unit is the recurring unit in the dispersant.In some embodiments, dispersant with same concentrations of two kinds of solution is fit to.
Can according to dispersant in selected solvent solvability and the convenience of Treatment Solution determine the upper limit of concentration of dispersant in solution.In one embodiment, the viscosity of each solution is less than about 50cps.In one embodiment, product solution can have the dispersant of about at the most 50% weight.As mentioned above, metal agent and the salt precursor solution dispersant that can have identical or different concentration.All wt % is based on the gross weight of all components in the solution.
In the present embodiment, metal agent and salt precursor separately metal agent and the concentration in the salt precursor solution preferably at least about 1500ppm to metal agent or salt precursor the upper solubility limit in selected solvent, in some embodiments is that about 5000ppm is to upper solubility limit, in some embodiments is about 5000ppm to 50,000ppm (5wt%), in other embodiment is about 5000 to about 20,000ppm (2wt%).
At room temperature mixed solution comprises that stirring may be favourable.Can use the mixing speed that produces whirlpool or quicker.The mixing speed of selecting should not cause solution loss in foaming, effervesce or the blender.Continue during interpolation to stir.
Can under the pressure of environmental pressure or reduction, mix.In some embodiments, mixing can cause solution foaming or effervesce.Effervesce or foaming are disadvantageous, because can cause higher concentration slaine bag to form, produce the granularity greater than desired particle size.Can use the pressure of reduction in these cases.This pressure can be that environmental pressure is to any pressure between the selected vapor pressure solvent.In one embodiment, when water was solvent, pressure can be environmental pressure to about 40mbar.
Select the adding rate of salt precursor and metal agent solution so that when mixing, keep settled solution.Can accept slight local muddiness, need only solution clarification when stirring.Can perusal or with the transparency of UV-VIS spectrum monitoring solution.Suitable adding rate can followingly be determined: preparation has one group of solution of desired concn, monitors the transparency of the solution of different adding rates.This embodiment of operating in 26-31 illustrates.Dispersant is included in the salt precursor solution also can allows adding rate faster.
In another embodiment, when needs faster during adding rate, allow metal agent and dispersant with before the salt precursor solution mixes in complex compound formation condition (comprising the complex compound formation time) mixing down.It is believed that dispersant forms complex compound with metal agent in metal agent solution.In the present embodiment, preferably before metal agent solution and the merging of salt precursor solution, allow metal agent and the complete complexing of dispersant." fully complexing " refer to basically all metal ions all with at least a dispersant complexing." basically all " refer at least about 90%, in some embodiments at least about 95% described metal ion and at least a dispersant complexing.
The available light spectrometry is as monitoring the complex compound formation time by UV-VIS or FTIR in solution.Measure non-dispersant metal agent solution spectrum.Monitor the metal agent solution spectrum after adding dispersant, the change of monitoring spectrum.The complex compound formation time is the time that spectrum changes platform.
Perhaps, can measure the complexing time from experience, formation has one group of metal agent-dispersant solution of same concentrations, allows each solution mixing different time (as 1,3,6,12,24,72 hour and 1 week), and each metal agent-dispersant solution is mixed with the salt precursor solution in batches.Do not control adding rate ground when metal agent and salt precursor solution and directly be not poured on together, the metal agent-dispersant solution of mixed complex formation time section will form settled solution.For example available 1 second or shorter time add 20ml metal agent solution in the 20ml salt precursor solution.
The complexing condition comprises the ratio and the stirring rate of complexing time (as above discussing), temperature, dispersant and metal agent.Increase the mol ratio and the stirring rate of temperature, dispersant and metal agent, will reduce the complexing time.Those skilled in the art will be with reference to the method for this paper, and the condition that can change is to obtain disclosed complexing level.
If metal agent and dispersant be complexing fully not, can select mixing condition to make the response bias in the mixture form dispersant-metal agent complex compound above the slaine that forms not complexing.This deflection can by control (a) dispersant in the solution that salt precursor or salt precursor and metal agent solution are added into concentration and (b) composite rate of metal agent and salt precursor solution realize.
In case hybrid metal agent and salt precursor solution can be with product solution dryings.Can use any conventional drying equipment such as freeze-dryer, spray dryer etc.Well known drying equipment and process.Suitable spray dryer example is the whirlwind spray dryer, as available from GEANiro, and Inc.For atomized drying, the temperature of spraying inlet is higher than the flash-point of selected solvent.
Freeze-dryer can comprise GEA Niro, Inc available from how tame manufacturer.Those skilled in the art know selection freeze drying temperature and pressure makes the solvent distillation.Can use any temperature in institute's choosing method normal ranges.
Desciccate solution, until the solvent of gained pulvis less than about 10% weight, in some embodiments less than about 5% weight, in some embodiments less than about 2% weight.When the solvent that is used to form stable metal salt was compatible with the reactant mixture that is used to form polymeric articles, higher solvent strength may be suitable.Pulvis contains stable slaine particulate, and the about at the most 100nm of its granularity, about 50nm at the most are at the about at the most 15nm of some embodiments, by being dispersed in the water, with transmission electron microscope, photon correlation spectroscopy or dynamic light scattering measurement.
Stable slaine pulvis directly can be added in the reactant mixture.Can be easy to calculate the amount of the stable metal salt powder that will add so that the antimicrobial metal ion of desired level to be provided.
Make the active mixture reaction that contains slaine to form antimicrobial polymeric articles.Those skilled in the art can be easy to the condition of choice reaction according to the component in the active mixture.For example, when antimicrobial polymeric articles was the contact lenses of usefulness free radical activity component formation, active mixture comprised initator, and reaction condition can comprise to be used up or heat cure.When antimicrobial metal salt is light sensitivity, during as AgI, AgCl and AgBr, slaine is exposed to is lower than the wavelength of above-mentioned critical wavelength Ag +Be converted into Ag 0, the articles for use blackening that causes mixing salt.Therefore, in one embodiment, when using the free radical activity component, be cured by being exposed to visible light.In other embodiments, active mixture also comprises at least a UV absorption compound, with visible light, heat or its combination and solidification.In also having other embodiment, active mixture also comprises at least a UV absorption compound, visible light light trigger, uses visible-light curing.
Slaine is formed at or adds in the multiple polymers.Can select suitable polymers according to desired use.For example for the packaging for foodstuff purposes, polymer such as PETG, high density polyethylene (HDPE) and polypropylene are usually used in the Food ﹠ Drink container, and low density polyethylene (LDPE) is usually used in the plastic wraps thing.
Several embedded type devices, as displaced type joint (joint replacement), with highly cross-linked ultra-high molecular weight polyethylene (UHMWPE) preparation, described poly molecular weight is usually at least about 400,000, in some embodiments is about 1,000,000 to about 10,000,000, limit melt index (ASTM D-1238) and be substantially 0 and the proportion that reduces greater than 8, be about 25 to 30 in some embodiments.
The example that is suitable as the absorbability polymer of the yarn for preparing suture and wound dressing includes but not limited to aliphatic polyester, include but not limited to that lactide (comprises lactic acid d-, a l-and a lactide), glycolide (comprising glycolic), 6-caprolactone, to dioxanone (1, the 4-dioxane-2-ketone), trimethylene carbonate (1, the 3-dioxane-2-ketone), the alkyl derivative of trimethylene carbonate, δ-Wu Neizhi, beta-butyrolactone, gamma-butyrolacton, ε-decalactone, butyric ester, hydroxyl valerate, 1,4-Dioxepane-2-ketone (comprises its dimer 1,5,8,12-four oxacyclotetradecane-7, the 14-diketone), 1,5-Dioxepane-2-ketone, 6,6-dimethyl-1, the homopolymer of 4-dioxane-2-ketone and copolymer and polymer admixture thereof.
The also available not absorbent polymeric material preparation of suture, described material is such as but not limited to polyamide (polyhexamethylene adipamide (nylon 66), polyhexamethylene sebacamide (NYLON610), polycaprolactam (polycapramide) (nylon 6), poly-lauramide (nylon 12) and poly-6I hexamethylene isoterephalamide (nylon 61) copolymer and admixture thereof), polyester is (as PETG, PA polybutyleneterephthalate (polybutyl terephthalate), its copolymer and admixture), fluoropolymer polymer (as polytetrafluoroethylene (PTFE) and Kynoar), polyolefin (comprises isotaxy and syndiotactic polypropylenes and admixture thereof as polypropylene, with serve as that the main admixture of forming with the blending of heterotactic polypropylene (as is described in and transfers Ethicon with isotaxy or syndiotactic polypropylenes, Inc. the United States Patent (USP) of issuing on December 10th, 1,985 4,557,264, this by reference in conjunction with) and the admixture formed with polyethylene blending (as be described in and transfer Ethicon, Inc. the United States Patent (USP) 4 that issue 10 days December in 1985,557,264) and the combination.
The body of tear stains plug (punctal plug) can include but not limited to silicone, silicone admixture, silicone copolymer (as the hydrophilic monomer of pHEMA (hemacol), polyethylene glycol, polyvinylpyrrolidone and glycerine) and silicon hydrogel polymer with any suitable biocompatible polymer preparation, for example be described in U.S. Patent number 5,962,548,6,020,445,6,099,852,6,367,929 and 6,822,016.Other suitable biocompatible materials for example comprises: poly-(ethylene glycol); Poly-(ethylene oxide); Poly-(propane diols); Poly-(vinyl alcohol); Poly-(methacrylic acid hydroxyethyl ester); Poly-(vinylpyrrolidone); Polyacrylic acid; Poly-(ethyl oxazoline); Poly-(DMAA); Phospholipid, for example PC derivative; Polysulfobetains; Polysaccharide and carbohydrate, for example hyaluronic acid, glucan, hydroxyethylcellulose, hydroxypropyl cellulose, gellan gum, guar gum, Heparan sulfate, chondroitin sulfate, heparin and alginates; Protein, for example gelatin, collagen, albumin and ovalbumin; Polyaminoacid; Fluorinated polymer, for example polytetrafluoroethylene (PTFE) (" PTFE "), Kynoar (" PVDF ") and Teflon (teflon); Polypropylene; Polyethylene; Nylon; With ethylene-vinyl alcohol (" EVA ").
The polymer moieties of supersonic operation instrument can be used polyimides, PEP (FEPTeflon), PTFE Teflon, silicone rubber, the preparation of EPDM rubber, wherein any all Available Materials such as Teflon or graphite-filled or do not fill.Example is disclosed in US20050192610 and US 6458142.
The preparation method of well-known above-mentioned polymer is by melt-blended or can be easy to mix stable slaine particulate in the polymerization process.By considering that dispersant and the dispersant-heat endurance of metal agent complex compound can be easy to select the suitable dispersant of each system.
In one embodiment, antimicrobial polymeric articles is an eyeglass.When being used for this paper, term " eyeglass " refers to be positioned at the Ophthalmoligic instrument on intraocular or the eye.These devices can provide vision correction, therapeutic action, beautification function or its combination.The term eyeglass includes but not limited to soft contact lens, hard contact lens, intraocular lens, covering eyeglass, eye insert (ocular insert) and optics insert (optical inserts), such as but not limited to the tear stains plug.
Soft contact lens can include but not limited to silicon hydrogel and fluorine hydrogel with silicone elastomer or hydrogel preparation.Preferred eyeglass visually-clear of the present invention, its visual clarity can be compared with the eyeglass that for example prepares with etafilcon A.
Slaine of the present invention can be added in the soft contact lens preparation, described preparation is described in U.S. Patent number 5,710, and 302, WO 9421698, EP 406161, JP 2000016905, U.S. Patent number 5,998,498, Application No. 09/532,943, U.S. Patent number 6,087,415, U.S. Patent number 5,760,100, U.S. Patent number 5,776, and 999, U.S. Patent number 5,789,461, U.S. Patent number 5,849,811 and U.S. Patent number 5,965,631.In addition, slaine of the present invention can be added in the commodity soft contact lens preparation.The soft contact lens examples of formulations includes but not limited to preparation etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, lotrafilcon A, lotrafilcon B, galyfilcon, senofilcon and comfilcon.In one embodiment, the contact lenses preparation is etafilcon A, balafilcon A, acquafilcon A, lotrafilcon A, lotrafilconB, senofilcon, galyfilcon, comfilcon, be etafilcon A in other embodiments, galyfilcon, comfilcon and silicon hydrogel, as be prepared in U.S. Patent number 5,998,498, Application No. 09/532,943, the continuation part of the Application No. 09/532,943 that on August 30th, 2000 submitted to, WO03/022321, U.S. Patent number 6,087,415, U.S. Patent number 5,760,100, U.S. Patent number 5,776,999, U.S. Patent number 5,789,461, U.S. Patent number 5,849,811 and U.S. Patent number 5,965,631.These patents and all are attached to herein by reference fully in the disclosed patent of this paragraph.In one embodiment, slaine of the present invention is added hydrophilic index at least about in 41 the lens materials, as be described in US 11/757484.In one embodiment, articles for use are the contact lenses that form with galyfilcon.
The hard contact lens polymer manufacture, include but not limited to the polymer of polymethylacrylic acid (methyl) ester, Si acrylate, silicone acrylate, fluorinated monomer, fluorine ether, polyyne and polyimides, wherein the preparation method of representative instance can consult United States Patent (USP) 4,330,383.Intraocular lens of the present invention can form with known materials.For example, eyeglass can prepare with rigid material, includes but not limited to poly-methyl methacrylate base ester, polystyrene, Merlon etc. and combination thereof.In addition, soft material be can use, hydrogel, silicone material, acryhic material, fluoro carbon materials etc. included but not limited to, or its combination.Typical intraocular lens is described in WO0026698, WO 0022460, WO 9929750, WO 9927978 and WO 0022459, U.S. Patent number 4,301,012,4,872,876,4,863,464,4,725,277,4,731,079.Slaine can be added as described above in the hard contact lens preparation and intraocular lens preparation.
Can be coated with biologic medical equipment (comprising ophthalmic lens) to increase itself and living tissue compatibility, prerequisite is the activity that described coating can not hinder or poorly reduce antimicrobial metal salt.Therefore, the available plurality of reagents that is used to be coated with eyeglass is coated with articles for use of the present invention.Perhaps, stable slaine particulate can be added easily in any known coating composition, in one embodiment, according to indication of the present invention, add in the liquid composite that forms with solution and active mixture, active coating transfer coated etc. as dip coating solution, mould.Suitable example includes but not limited to use the coating of coupling agent or tack coat (as to be disclosed in U.S. Patent number 6,087,415 and US 200//0086160), potential hydrophilic coating (as is disclosed in 5,779,943), PEO star coating (as is disclosed in 5,275,838), the covalent bond coating (as is disclosed in 4,973,493), by activated monomer polymerization that contacts articles for use to be coated and the coating (as being described in 5,135,297) that is cross-linked to form, the glycerol polymerization coating (as is disclosed in 6,200,626), nonactive or complex compound forms coating and (as is disclosed in EP 1,287,060, US 6,689,480 and WO2004/060431), " layered coating " (as is disclosed in EP 1252222, US7022379, US 6,896, and 926, US 2004/0224098, US2005058844 and US 6827966), mould transfer coated (as being disclosed in WO03/011551A1) and surface modification process (are disclosed in 5,760,100).Silicate coating (as being disclosed in 6,193,369) and plasma-coated (as being disclosed in 6,213,604) can be coated in articles for use as on the Ophthalmoligic instrument that contains antimicrobial metal salt.These applications and patent are attached to by reference and are used for those programs, composition and method herein thus.
Many eyeglass preparations mentioned above can allow the user continuous 1 day to the 30 days time to embed eyeglass.Known eyeglass is of a specified duration more within the eye, and bacterium and the chance of other germs collect on those lens surfaces are big more.Eyeglass of the present invention helps preventing that bacterium from accumulating on polymeric articles such as the contact lenses.
And, the present invention includes and reduce and the troop method of on the eyeglass that places the mammal eye relevant adverse events of microorganism, comprise following steps, formed or be made up of following steps substantially by following steps: the antimicrobial eyeglass that will contain at least a antimicrobial metal salt placed on the mammal eyes at least about 14 days, and wherein said eyeglass comprised the extractible antimicrobial metal at least about 0.5 μ g at least after described 14 days time periods.In another embodiment, eyeglass comprised the described extractible antimicrobial metal at least about 0.5 μ g after at least 30 days.In the present embodiment, lenses fitted continuously, perhaps the mode that can wear daytime is worn (take off before sleeping, embed after waking up again).Available above-described condition is measured the antimicrobial metal salt that extracts.In also having another embodiment, eyeglass of the present invention comprises the antimicrobial metal salt that is enough to wear in expection the initial concentration that discharges 0.5 μ g antimicrobial metal every day phase.The expection phase of wearing is the time span of recommending the patient wear eyeglass.
Term eyeglass, antimicrobial eyeglass and slaine all have their above-mentioned implication and preferable range.Phrase " with the microorganism relevant adverse events of trooping " includes but not limited to contact ophthalmia, contact lenses correlation periphery ulcer, contact lenses correlation blood-shoot-eye illness, wellability keratitis, microorganism keratitis etc.Term mammal refers to vertebrates such as any homoiothermy height, and preferred mammal is the people.
Use following method of testing in an embodiment.
Silver content with eyeglass behind instrumental neutron activation analysis " INAA " the mensuration autoclaving.INAA is a kind of qualitative and quantitative elemental analysis method, by using the neutron exposure artificial induction specificity radionuclide in the nuclear reactor.The characteristic gamma-rays that the radionuclide of quantitative measurment decay sends behind the irradiation sample.Owing to have high degree of specificity, there is specific radionuclide in the gamma-rays prompting that detects in particular energy.Becker，D.A.；Greenberg，R.R.；Stone，S.F.J.Radioanal.Nucl.Chem.1992，160(1)，41-53；Becker，D.A.；Anderson，D.L.；Lindstrom，R.M.；Greenberg，R.R.；Garrity，K.M.；Mackey，E.A.J.Radioanal.Nucl.Chem.1994，179(1)，149-54。The INAA program that is used for quantitative contact lens material silver and iodide content is used following two kinds of nuclear reactions:
1. in priming reaction, catch the radioactivity neutron that nuclear reactor produces after, with stable 109Ag produces 110Ag is with stable 127I produces 128I.
2. in decay reaction, 110Ag (τ 1/2=24.6 seconds) and 128I (τ 1/2=25 minutes) mainly by decaying with the proportional negatron emission of initial concentration, energy relative radioactivity nucleic is distinctive (Ag is that 657.8KeV and I are 443KeV).
Gamma-rays emission is to irradiation 110Ag and 128The decay of I is specificity.With gamma-ray spectroscopy method (the pulse height analyze technology of having established) measurement standard product and sample, the concentration of Measurement and analysis thing.
Following measurement turbidity: at ambient temperature the hydration testing lens is placed in the BBS of transparent 20 * 40 * 10mm aquarium, this aquarium is positioned at smooth black background top, its below optical fiber lamp (Titan Tool Supply Co. optical fiber lamp, 0.5 " diameter photoconduction; setting power is 4-5.4) irradiation; direction of illumination is orthogonal to the eyeglass pond with 66 ° of angles; obtain the eyeglass image with the video camera (DVC 1300C:19130RGB camera has Navitar TV Zoom 7000 zoom eyeglasses) that places eyeglass platform top 14mm from the top perpendicular to the eyeglass pond.Deduct the image of blank pool, subtracting background scattering from the eyeglass scattering with EPIX XCAP V 1.0 softwares.The scattered light image that quantitative analysis deducts, the 10mm of integration eyeglass central authorities is then with-1.00 diopter CSI Thin
Figure A20078004897700281
(setting turbidity value arbitrarily is 100, and setting turbidity value during no eyeglass is 0) relatively.Analyze 5 eyeglasses, the result is on average obtained turbidity value, be the percentage of standard C SI eyeglass.
With the wide-open Nikon SMZ1500 of " dark field " pattern and aperture microscope subjective measurement turbidity.Eyeglass to be assessed is placed the glass Petri culture dish that SSPS is housed, be contained in then on the microexamination platform.The qualitative value of this method roughly is equivalent to the turbidity percentage above measured, and is as follows:
" high turbidity ":＞～100%
" low turbidity ":＜～70
" extremely low turbidity ":＜～40%
Following measurement color: at room temperature make sample balance in borate buffering sodium sulphate packaging solution (SSPS).Remove the excessive moisture of lens surface.Eyeglass is placed on the microslide, flatten with sponge brush.A packing liquid is placed on the eyeglass, cover second microslide, guaranteeing does not all have bubble above or below the eyeglass.Make eyeglass placed in the middle before the white background on the X-Rite Model SP64 colorimeter aperture of equipment QA Master 2000 softwares.With 1DAYACUVUE contact lenses calibration instrument.Obtain 3 readings, report mean value.By above-mentioned test, measure the L of DAY ACUVUE contact lenses *a *b *Be worth 6 times, mean is: L *=72.33 ± 0.04, a *=1.39 ± 0, b *=0.38 ± 0.01.
UV-Vis spectrum with UVICAM UV300 apparatus measures active mixture.Data with single sweep and 1.5nm bandwidth collection 200-800nm.Used baseline solvent is listed in each embodiment.Original data record is used for drawing and analysis in Excel.With the standardization of spectrum relative wavelength, drawing compares.For the argentiferous monomer, add and to contain behind the silver components 24 hours and obtain the UV-Vis data.
With the Perkin Elmer Lambda 19UV/VVIS scanning pectrometer (twice monochromator system) of balance in the UV-VIS spectrum (at the transmission % of 200-800nm) of 200-800nm scope with 1nm interval acquiring eyeglass, be set as follows: the 4nm crack, the 960mn/min sweep speed, smoothly=2nm, NIR sensitivity=3, lamp variation=319.2nm, detector variation=860.8nm.Eyeglass is lain on circular sample frame and the folder, gauffer and stretching, extension are minimized.Eyeglass and specimen holder are placed in the Xiao Chi that packaging solution is housed, and curve (front curve) is in the face of sample beam (sample beam) before directed the making.Calculate spectrum with the software that is included in the instrument, use formula: %T Ave=S/N, wherein S is the summation at specific region %T, N is a number of wavelengths.
Measure slaine in plastic articles distribution everywhere with the electron probe microanalysis that is described in embodiment 23.
With laser light scattering or dynamic light scattering measurement granularity.For the sample of particle size range, use Horiba-LA930 laser diffraction granularity analyzer greater than about 500nm.Instrument detecting begins to carry out from the %T value of blank.The introducing of 1mL sample solution is contained in the circulation bath of 150mL water as medium.Using relative index of refraction is 5 as 1.7-0.1i and circulation rate.Sample ultrasonic was handled 2 minutes before measurement with ultrasonic in the instrument.Use during analysis
Figure A20078004897700301
X-100 (available from UnionCarbide) (0.1%) is as surfactant.Carry out 3 times and analyze, relatively trace (traces) is consistent each other to guarantee them.The report that instrument provides comprises the numerical value of particle size distribution figure and particle mean size.
For the sample of particle size range, use Malvern 4700 dynamic light scatterings less than about 500nm.Can draw (traceable) normal size ps particle with NIST before the sample analysis and carry out instrument detecting.The 1ml samples with water is diluted to 20ml, to sample sonication 1 minute, makes relative index of refraction and viscosity number all in the Input Software with Branson Ultrasonic probe.The report that instrument provides comprises the numerical value of particle size distribution figure and particle mean size.
Effect in order to the following method assessment anti-staphylococcus aureus of eyeglass (S.aureus).Make staphylococcus aureus clinical separation strain 031 (Staphylococcus aureus Clinical Isolate 031) culture grow overnight in tryptic soy medium (TSB).Culture is inferior with phosphate buffered saline (PBS) (PBS, pH=7.4 ± 0.2) washing 3 (3), the bacterial precipitation thing is suspended among the 10mL 2%TSB-PBS again.The preparation bacterial inoculum obtains final concentration and is about 1 * 10 8Individual colony-forming units/mL (cfu/mL).Serial dilution obtains inoculum concentration in 2%TSB-PBS be 1 * 10 4Individual cfu/mL.
Aseptic contact lenses are being changed in three times the 30mL phosphate buffered saline (PBS) (PBS, pH=7.4+/-0.2) flushing to remove residual solution.The contact lenses of each flushing are put into the independent instrument connection of sterile tissue culture plate with 500 μ L bacterial inoculums, then in oscillator-incubator (100rpm) in 35+/-2 ℃ rotation 20+/-2 hour.Each eyeglass and corresponding cell suspension are taken out in each hole, place 9.5mL to contain 0.05% (w/v) Tween TMAmong 80 the PBS (TPBS).
Make eyeglass and corresponding cell suspension with 1600rpm vortex 3 minutes then, the remaining bacteria that sticks on the eyeglass is separated with centrifugal force.With standard dilution with read plate technique and calculate bacterium alive in the gained supernatant.Calculate the recovery bacterium result's alive who links with eyeglass mean value.
In order to explain the present invention, the following example is included.These embodiment do not limit the present invention.They only are used for prompting and implement method of the present invention.Contact lenses specialty and other technical professional can find to implement other method of the present invention.But those methods are considered as within the scope of the invention.
Embodiment
Use following abbreviation in an embodiment
AHM=methacrylic acid 3-allyloxy-2-hydroxy-propyl ester
AMBN=2,2 '-azo two (2-methylbutyronitrile)
The BHT=Butylated Hydroxytoluene
The product of Blue HEMA=4 reactive blue and HEMA, as be described in embodiment 4 or U.S. Patent number 5,944,853
CGI 1850=1-hydroxycyclohexylphenylketone and two (2,6-dimethoxy benzoyl)-2,1: 1 (w/w) admixture of 4-4-tri-methyl-amyl phosphorous oxide
Two (2,4, the 6-the trimethylbenzoyl)-phenyl phosphorous oxide of CGI 819=
DI water=deionized water
DMA=N, the N-DMAA
DAROCUR 1173 2-hydroxy-2-methyl-1-phenyl-third-1-ketone
The EGDMA=ethylene glycol dimethacrylate
HEMA=methacrylic acid hydroxyethyl ester
The BAGE=glyceryl borate
The IPA=isopropyl alcohol
The MAA=methacrylic acid
The macromonomer that contains silicone of Macromer=such as embodiment 22 preparations
The dimethyl silicone polymer (MW800-1000) of mPDMS=list-methacryloxypropyl end
Norbloc=2-(2 '-hydroxy-5-methyl base acryloxy ethylphenyl)-the 2H-BTA
HO-mPDMS=list-(3-methacryloxy-2-hydroxypropyl oxygen base) dimethyl silicone polymer propyl group end, the monobutyl end (MW 612) is as embodiment 21 preparations
The AgI particulate that the synthetic embodiment 3 of AgI particulate-basis forms
The every gram dry lens of ppm=a few millionths microgram sample
PAA=polyacrylic acid (Mw 2000)
The PVP=polyvinylpyrrolidone
The PVA=polyvinyl alcohol
SiMMA=3-methacryloxy-2-hydroxypropyl oxygen base) two (trimethylsiloxy) methyl-monosilanes of propyl group
SSPS=borate buffering sodium sulphate packaging solution, following description preparation
The TAA=tert-pentyl alcohol
TBACB=3-chlorobenzoic acid tetrabutylammonium
The THF=oxolane
TRIS=3-methacryloxypropyl three (trimethylsiloxy) silane
W/w=weight/gross weight
W/v=weight/cumulative volume
V/v=volume/cumulative volume
It is standby to prepare following composition
Tear sample fluid (TLF) buffer solution:
(Sigma is S8875) with 0.01g D-glucose (Sigma, G5400) PBS of adding calcic and magnesium (Sigma, D8662) interior preparation tear sample fluid cushion liquid (TLF Buffer) with the 0.137g sodium bicarbonate.At room temperature stir the TLF buffer solution and dissolve (about 5 minutes) fully until component.
At about 60 ℃ and well-beatenly simultaneously following lipid is mixed about 1 hour until clarification in TLF Buffer, prepare lipid stoste:
Linoleic acid cholesteryl ester (Sigma, C0289) 24mg/mL
Linalyl acetate (Sigma, L2807) 20mg/mL
Triolein (Sigma, 7140) 16mg/mL
Oleic acid propyl ester (Sigma, O9625) 12mg/mL
Undecenoic acid (Sigma, U8502) 3mg/mL
Cholesterol (Sigma, C8667) 1.6mg/mL
Lipid stoste (0.1mL) and 0.015g mucin (from the mucin (Sigma, M3895, Type 1-S) of ox submaxilary) are mixed.3 parts of 1mL TLF Buffer are added in the lipid mucin mixture.Agitating solution is until all components dissolving (about 1 hour).Add capacity TLFBuffer and reach 100mL, fully mix.
According to listed order following component gradation is added in the 100mL lipid-mucin mixture of above preparation.Total about 1 hour of interpolation time.
Acidifying glycoprotein (Sigma, G3643) 0.05mg/mL from the ox blood slurry
Hyclone (Sigma, F2442) 0.1%
Gamma Globulin (Sigma, G7516) 0.3mg/mL from the ox blood slurry
Beta lactoglobulin (milk lipocaline) (Sigma, L3908) 1.3mg/mL
From the white lysozyme of egg (Sigma, L7651) 2mg/mL
Lactoferrin (Sigma, L4765) 2mg/mL from colostrum
Allow gained solution 4 ℃ of standing over night.With 1N HCl with pH regulator to 7.4.Filtering solution, be stored at-20 ℃ standby.
Borate buffering sodium sulphate packaging solution (SSPS)
The deionization H of packaging solution 2Comprise following ingredients among the O:
0.18% weight Boratex [1330-43-4], Mallinckrodt
0.91% weight boric acid [10043-35-3], Mallinckrodt
1.4% weight percent sulfuric acid sodium [7757-82-6], Sigma
0.005% weight methyl ether cellulose [232-674-9] is from Fisher Scientific
Embodiment 1
The solution of preparation 12.6g 5%PVP (K12) in DI water.Add 3.94g 1% liquor argenti nitratis ophthalmicus, at room temperature mixed 5 minutes with magnetic stirring bar.Add 3.47g 1% IodineSodium Solution then, at room temperature mixed 5 minutes with magnetic stirring bar.Obtain transparent silver iodide Nanodispersion.
Comparing embodiment 1
At room temperature with 1.0g 1%AgNO 3Solution adds in the 1.0g 1%NaI solution.Obtain containing the very muddy dispersion of AgI precipitation.Add 5g 5%PVP (K12) solution then, mixed 48 hours with magnetic stirrer.Sediment is complete obiteration not.
Embodiment 2
Repeat embodiment 1, but (Dallas Texas) replaces PVP (K12) to prepare starting soln for Celvol 09-523, CelaneseChemicals with the PVA of 98% hydrolysis.Obtain transparent Nanodispersion.
Synthetic embodiment 1
The mixture of following compounds packed into be equipped with in 5 liters of glass reactors of agitator, temperature control and cooling and heating outer cover.
Component Wt (gram)
Ethanol 2708.4g
HEMA 291.95g
MAA 5.96g
Norbloc 2.92g
Blue HEMA 0.0602g
TMPTMA 0.30g
Make temperature of reactor rise to 71 ℃, add 2.11g AMBN.The AMBN dissolving, using slowly, nitrogen stream covers reactor.Temperature was kept 20 hours at 71 ℃.
Prepare 51 liter of jars that has screw cap and be equipped with magnetic stirring bar, crude product is poured in the jar into every jar of 600g.With water-bath solution is heated to 60 ℃, constantly stirs with magnetic stirrer simultaneously.Then, add 54g heptane (9%), solution is heated to 60 ℃ again.Stop to stir, jar is placed 60 ℃ of water-baths.Made temperature drop to 24 ℃ gradually with 20 hours.The top is the fluid of clarification mutually now, and the end is semi-solid mutually.Top maximum mutually (about 80% total jar) but polymer solids content low (about 1.5-2.5%).
Remove the top phase of each jar, the end is dissolved in the hydrous ethanol mutually again, obtain the 2125g polymer solution, have following feature: 12% solid and 3% water.
Mini spray drier (Mini Spray Dryer) this solution of B-290 atomized drying with being equipped with inertia loop (Inert Loop), outlet filter (Outlet Filter) and efficient cyclone device (High Performance Cyclone), use following parameter:
Inlet temperature The inertia loop Outlet temperature The spraying flow velocity Aspirator Pump
120℃ -20℃ 50℃ 30mm 80％ 65％
This obtains meticulous white, bulky powder that 250g about 97% does.With powder transfer (about 77 grams of each flask) to a plurality of 1 liter of flask that are equipped with magnetic stirring bar.Flask is spent the night with further drying material 100-130 ℃ of application of vacuum under less than the vacuum pressure of 30mbar.
Morning next day, destroy vacuum with dry argon gas atmosphere, flask is transferred in the box with control drying nitrogen.The gross weight of flask is measured in the cooling back.In each 1 liter of flask, add 300g NMP (anhydrous N-Methyl pyrrolidone; Special pure; Anhydrous; Through molecular sieve, available from Fluka) with complete dissolved powders, check the uniformity of flask.The MAH (methacrylic anhydride 98% is pure) that weighs in 50cc glass cylinder container adds 50g NMP dilution MAH, shifts then.With other 50g NMP flushing glass cylinder container, guarantee to shift fully.Directly add triethylamine (puriss p.a. is available from Fluka) with the finn pipettor.Cover tight lid, use rubber belt sealing, cut off nitrogen stream.Allow reaction carry out about 40 hours.
The above following purifying of Zhi Bei polymer.The 75g polymer is dissolved among the 400mL NMP.In 25 liters of glass beakers, respectively pack into 4 liters of DI water, 30mL be fuming HCl (hydrochloric acid) and magnetic stirring bar.Each 200mL of functionalized products of last reaction is poured in the beaker gradually with the speed of about 10mL/sec.Precipitation occurs, remove water.The polymer that residue expands is dissolved in the 300mL ethanol again.
In other 25 liters of glass beakers, respectively pack into 4 liters of DI water and magnetic stirring bar.Polymer/ethanolic solution is poured in 25 liters of glass beakers that 2 * 4L DI water is housed, occurred precipitation again.Remove water, add fresh DI water, with the residual HCl of further extraction.Remove water after about 12 hours, measure the weight (about 120 grams) of expanded polymer material.
Expanded polymer materials tend is dissolved in the ethanol again, and obtaining solids content % is 13 ± 0.5%, then with 25mm GD/X 0.45 μ m Whatmann filter filtering solution.With the mini spray drier B-290 spray drying soln that is equipped with inertia loop, outlet filter and efficient cyclone device.Use following parameter:
Inlet temperature The inertia loop Outlet temperature The spraying flow velocity Aspirator Pump
79℃ -20℃ 43℃ 30mm 80％ 26％
This obtains the meticulous white bulky powder of about 155g.
Embodiment 3
The copolymer (3.49g) that makes synthetic embodiment 1 preparation and 4.9g masterbatch solution (contain 99.89% propane diols as thinner, two (acyl group) phosphine oxides of 1.10% dimethoxy benzoyl as light trigger and 0.011%4-metoxyphenol as inhibitor) mix.The 2g Nanodispersion of embodiment 1 preparation is weighed, mix with copolymer/masterbatch solution.Make the gained mixture with centrifugal 15 minutes of 2500rpm to remove the air of delay.Obtain transparent prepolymer.
Prepolymer is distributed in the thermoplastic contact lenses mould (the front and rear curved face prepares with polystyrene) that outgased 12 hours under nitrogen.Under 20 ℃ of room temperatures and air, use 30mW/cm 2Prepolymer in the luminous intensity irradiation mould 30 seconds.With eyeglass hydration 20 minutes in 20 ℃ of DI water, packing in borate buffering sodium sulphate packaging solution (SSPS) was sterilized 18 minutes at 121 ℃ then.Under dark-field microscope, observe eyeglass and have low-down turbidity.The average silver content of measuring 5 eyeglasses with neutron activation technique is 9.72 micrograms, and standard deviation is 0.16 microgram/eyeglass.
Embodiment 4
Mix 10 minutes in the 1%NaI solution with 0.339g PVP (K12) powder adding 3.487g to form the salt precursor solution A.PVP (K12-0.266g) is slowly added 4.29g 1%AgNO 3Solution is interior to form the metal agent solution B.To mix 3 minutes in salt precursor solution A (0.379g) the adding 17.603g monomer mixture that hereinafter table 1 shows.Then metal agent solution B (0.3963g) is added in the monomer mixture and stirred 10 minutes.
Make monomer mixture vacuum (29 " Hg) degassing 20 minutes.Monomer mixture is dispensed in the thermoplastic contact lenses mould (the front and rear curved face prepares with polystyrene), under room temperature and nitrogen, uses 5mW/cm 2 Luminous intensity irradiation 6 minutes.With eyeglass hydration in 20 ℃ of DI water, in SSPS, pack about 20 minutes of 121 ℃ of autoclavings then.Under dark-field microscope, observe eyeglass and have low-down turbidity.Measuring silver content with neutron activation technique is 4.7 micrograms, and standard deviation is 0.11 microgram/eyeglass.
Table 1
Component Parts by weight
HEMA 58.08
MAA 0.96
Blue HEMA 0.07
EGDMA 0.71
Darocur 1173 0.14
BAGE 40
Embodiment 5
(K12 0.946g) slowly adds in the active mixture that 30.7g table 1 lists mixed dissolution 25 minutes with PVP.Add 0.0177g AgNO 3(solid) also mixes until dissolving.Add 0.0300g NaI (solid) then, at room temperature mixture is mixed the active mixture that contained particulate in 1 hour with formation.Make and contain particulate active mixture vacuum (29 " Hg) degassing 10 minutes.Make to contain the particulate active mixture and be distributed in the contact lenses mould (the front and rear curved face prepares with polystyrene), describe curing, hydration, packaging sterilizing according to embodiment 4.Under dark-field microscope, observe eyeglass and have low-down turbidity.Measuring silver content with neutron activation technique is 12.8 micrograms, and standard deviation is 0.4 microgram/eyeglass.
Embodiment 6-13
In the following example, prepare 2 kinds of mixtures respectively.The listed active mixture of table 1, PVP (K12) and the NaI of the amount of listing by mixture table 2 prepare salt precursor mixture (" SPM ").Listed PVP concentration (wt%) is represented with the weight % of PVP in containing the particulate active mixture.The listed active mixture of table 1 and the AgNO of the amount of listing by mixture table 2 3Preparation metal agent mixture (" MAM ").Mix various mixtures until mixing all components, form transparent mixture (about 5 to about 19 hours).In each embodiment, the salt precursor mixture SPM of about equal volume and metal agent mixture M AM are mixed to form active mixture, NaI and AgNO in this active mixture 3Mol ratio show at table 3 the 2nd row.Various active mixtures were mixed 〉=30 minutes, but embodiment 8 mixed 1 hour.Active mixture is outgased under the listed condition of table 3.According to the description of embodiment 4 active mixture distribution, curing, hydration, packaging sterilizing with the various degassings.Under dark-field microscope, measure the turbidity of eyeglass.Measure silver content with neutron activation technique.Target silver absorptive amount all is about 10 μ g in all eyeglasses.Result's table 3 hereinafter shows.
Table 2
Ex# gm NaI /SPM gm RMM /SPM gm AgNO 3 /MAM Gm RMM/ MAM [PVP] (k12) (wt％)
6 0.11 29.6 0.067 35 0.5
7 0.051 40 0.42 40 1
8 0.017 20 0.02 20 1.6
9 0.017 20 0.03 20 0.5
10 0.019 20 0.04 20 0.6
11 0.73 261 0.2 269 0.1
12 0.039 40 0.04 40 2.6
13 0.039 40 0.04 40 2.6
Table 3
Embodiment number NaI∶AgNO 3Mole [PVP](k12) (wt％) Dt The slaking condition Turbidity before the sterilization Sterilization back turbidity Colour of lens
6 1.9 0.5 5 N/A Extremely low Low Normally
7 1.4 1 5 N/A Extremely low Low Normally
8 0.98 1.6 5 N/A Extremely low Low Yellow
9 0.71 0.5 5 N/A Extremely low Low Light brown
10 0.58 0.6 5 N/A Extremely low Low Brown
11 4.1 0.1 5 N/A Extremely low Extremely low Normally
12 1.1 2.6 50 N/A Extremely low High Normally
13 1.1 2.6 50 70℃ 20min Extremely low Low
Dt=outgases the time, minute
Embodiment 6 and 7 turbidity before sterilization that comprises molar excess NaI is extremely low, and the turbidity after the sterilization is low, has normal color.By contrast, with the same terms preparation but have excessive AgNO 3Embodiment 8,9 and 10 present yellow, light brown and brown respectively.Therefore, embodiment 6 and 7 shows and to guarantee that processing conditions that metal agent is converted into slaine provides the articles for use of color improvement, particularly when metal agent is stronger than the light sensitivity of slaine.
Embodiment 12 turbidity before sterilization that has 2.6%PVP and degassing step and be 50 minutes is extremely low, but sterilization back turbidity height, the particulate slaking may take place in prompting when sterilization.But when adding particulate maturation stage (embodiment 13,70 ℃ 20 minutes) before the curing activity mixture, the gained eyeglass shows after sterilization and hangs down turbidity.
Embodiment 14
Prepare the hereinafter active mixture of table 4.Active component is represented that with the percetage by weight of all active components (not comprising thinner) thinner is represented with the percetage by weight of end reaction mixture.With AgNO 3Solid (0.040g) adds in the 28.09g monomer mixture.(solid 0.0427g) adds in the mixture, at room temperature mixes 1 hour with NaI then.After the mixing, still have solid at container bottom.(the front and rear curved face is used to make active mixture be distributed in thermoplastic contact lenses mould
Figure A20078004897700391
The preparation, available from Zeon, Corp.) in, at room temperature and N 2Under use 5mW/cm 2 Luminous intensity irradiation 10 minutes.With eyeglass hydration in 25 ℃ of DI water, in borate buffering sodium sulphate packaging solution, pack about 20 minutes of 121 ℃ of autoclavings.The turbidity of observing eyeglass under dark-field microscope is extremely low, but has slight light/dark balance.Measuring silver content with neutron activation technique is 6.2 micrograms, and standard deviation is 0.21 microgram/eyeglass.
Table 4
Component
SiMMA 30
PVP(K90) 6
DMA 31
MPDMS 23
HEMA 7.5
Norbloc 1.5
CGI 819 0.23
EGDMA 0.75
Blue HEMA 0.02
PVP(MW 2,500) 11
TAA 29
Embodiment 15
While stirring PVP K12 (9.29g) is slowly added in the 200.00g TPME, mixed 20 minutes.0.7040g silver nitrate solid is added in the solution to form metal agent solution then.Stirred metal agent solution 6 hours with magnetic stirrer.
Sodium iodide (0.8880g) is added formation salt precursor solution in the 200.13g TPME.Stirred the salt precursor solution 6 hours with magnetic stirrer.Constantly stirring is mixed in the salt precursor solution (171.21g) metal agent solution (170.89g).Obtain transparent Nanodispersion.Solution was mixed 25 minutes.Total Nanodispersion is mixed in the 500.20g active mixture that hereinafter table 5 is listed.
Table 5
Component Parts by weight
SiMMA 30.00
mPDMS1000 22.00
DMA 31.00
HEMA 8.50
EGDMA 0.75
PVP K90 8.00
Norbloc 1.50
Blue HEMA 0.02
CGI 819 0.23
" (740mm) the Hg degassing is 15 minutes to make active mixture-29.(the front and rear curved face is used to make active mixture be distributed in thermoplastic contact lenses mould
Figure A20078004897700401
The preparation, available from Zeon, Corp.) in, under room temperature and nitrogen, use 5mW/cm 2 Luminous intensity irradiation 6 minutes.Then with eyeglass hydration 30 minutes in 20 ℃ of DI water, then hydration 60 minutes in 70%IPA, rinsing 1 minute in DI water then places DI water＞2 hour then, all at room temperature carries out.Check eyeglass, in SSPS, pack, 121 ℃ of autoclavings 18 minutes.
The average silver-colored absorptive amount of eyeglass is 10.70ug, and standard deviation is 0.2ug (5 eyeglass).The eyeglass turbidity is 68%, and standard deviation is 8.9% (5 eyeglass).
Embodiment 16:
The component of listing with table 6 prepares the 419.5g active mixture.
HEMA added form HEMA/TPME (HEM: TPME 5.1: 10) solution among the TPME, in the amber bottle of cleaning, mixed 1 hour.
With stirring in the 70.0g HEMA/TPME solution in slowly adding cleaning of 7g PVP (K12) amber bottle and with magnetic stirring bar, form the metal agent mixture.The hybrid metal agent composition all dissolves until all PVP (K12).Add AgNO 3(0.49g) mix and to dissolve until all solids in 6 hours.
In the 30g HEMA/TPME solution in the 0.42g NaI adding amber bottle, all dissolved until all solids in 6 hours with the magnetic stirring bar mixing, form the salt precursor mixture.
While stirring metal agent (67.02g) mixture is slowly poured in the salt precursor mixture, mixed 1 hour.Obtain containing the transparent dispersion of slaine AgI.
The active mixture that preparation has the listed component of table 6.Active component (419.5g) is mixed in amber bottle with slaine dispersion (80.5g), mix above about 24 hours." degassing is 15 minutes under the Hg to use 3 μ g filter filter activity mixtures then ,-29.
Table 6
Component Parts by weight
SiMMA 18
MPDMS1000 13.2
DMA 18.6
Tert-pentyl alcohol 29
EGDMA 0.45
Norbloc 0.9
Blue HEMA 0.012
CGI 819 0.138
PVP K90 3.6
(the front and rear curved face is used to make active mixture be distributed in thermoplastic contact lenses mould
Figure A20078004897700411
The preparation, available from Zeon, Corp.) in, under room temperature and nitrogen, use 5mW/cm 2 Luminous intensity irradiation 6 minutes.Then with eyeglass hydration 30 minutes in 20 ℃ of DI water, then hydration 60 minutes in 70%IPA, rinsing 1 minute in DI water is then left standstill in DI water＞2 hours, all at room temperature carries out.Check eyeglass, in borate buffering sodium sulphate packaging solution, pack, 121 ℃ of autoclavings 18 minutes.
The average silver-colored absorptive amount of eyeglass is 10.60ug, and standard deviation is 0.2ug (5 eyeglass).The eyeglass turbidity is 38.6%, and standard deviation is 4.3% (5 eyeglass).
Embodiment 17
0.0243g PVP K12 is slowly added in the 10.0037g TPME, mixed 20 minutes with magnetic stirrer.Then the 0.0199g silver nitrate is added in the solution, solution is mixed obtained solution A in 4 hours.0.054g sodium iodide solid is added in the 10.0326g TPME, at room temperature mix obtaining solution B in 4 hours.Solution A is poured in the solution B, mixed 20 minutes to obtain silver iodide transparent Nanodispersion in TPME.
The silver iodide Nanodispersion for preparing more than the 4.20g is added 5.13g have in the monomer mixture of hereinafter forming shown in the table 7, mixed 12 hours." the Hg vacuum outgas 20 minutes that makes monomer then 22.(the front and rear curved face is used to make active mixture be distributed in thermoplastic contact lenses mould
Figure A20078004897700421
The preparation, available from Zeon, Corp.) in, under room temperature and nitrogen, use 5mW/cm 2 Luminous intensity irradiation 6 minutes.Then with eyeglass hydration 30 minutes in 20 ℃ of DI water, then hydration 60 minutes in 70%IPA, rinsing 1 minute in DI water is then left standstill in DI water＞2 hours, all at room temperature carries out.Check eyeglass, in borate buffering sodium sulphate packaging solution, pack, 121 ℃ of autoclavings 18 minutes.
The silver content of eyeglass is 12ug, and standard deviation is 0.1ug (5 sample).Turbidity is 84%, and standard deviation is 4 (5 samples).
Table 7
Component Parts by weight
HO-mPDMS 55％
DMA 19.53％
HEMA
8％
TEGDMA 3％
Norbloc 2.2％
PVP K90
12％
Blue HEMA 0.02％
CGI 819 0.25％
Comparing embodiment 2
With the galyfilcon eyeglass of curing and hydration, be ACUVUE available from the Vistakon trade mark
Figure A20078004897700422
Contact lenses, place in the deionized water of blister package.Remove excessive deionized water, 0.8mL salt precursor mixture (1100ppm NaI is in DI) is added in the bubble-cap of dress eyeglass, at room temperature standing over night.Remove the precursor mixture that desalts, add 0.8mL metal agent mixture (700ppm silver nitrate and 5%PVP (k90)/DI).Remove metal salt mixture after 3 minutes, deionized water (900 μ L) is added in the bubble-cap, left standstill about 5 minutes, finally remove.Repeat deionized water again and handle 2 times, eyeglass is transferred in the vial that SSPS is housed.With vial sealing, 122 ℃ of autoclavings 30 minutes.Analyze eyeglass with INAA, comprise about 16 μ g Ag.
Embodiment 18 and comparing embodiment 2
The relative silver content of measuring embodiment 6 and comparing embodiment 2 eyeglasses with EPM distributes to determine contact lenses silver content everywhere.
The preparation sample is used for side (profile) to be analyzed, and whole eyeglass vertically is contained in the 25mm diameter aluminum frame, and this aluminium frame cuts at half place, holes and has screw thread, clamps sample for 2 machine screws nails.Clamp eyeglass so as half of material in aluminium frame surface.Stably impose uniformity without examining individual cases with clean monolateral razor then and start shooting half of sheet to avoid tearing the cutting surface.Then these samples are coated with carbon to guarantee conductivity in cold boiler.The distal edge that is coated with these samples with colloidal-carbon coating makes conductivity better then.
Downcut near remaining the rectangular of half optic diameter from remaining half eyeglass, be placed on carefully on the 25mm diameter support, two bilateral carbon " adhesive tab " are arranged on the end face, concave upright.
Remaining lens materials string convex surface upwards is fixed on two " adhesive tab " goes up analysis lens nonreentrant surface.With clean Teflon material piece (.032 " thick) contact lenses flatly are pressed in carbon " adhesive tab " on.These samples are used 20-40nm Spec-Pure equadag coating in the carbon cold boiler.The distal edge that is coated with these samples with colloidal-carbon coating makes conductivity better.
With Cameca SX-50 (1988) with 4 wavelength spectrometers or SX-100 (2005) automation electron microprobe analysis sample, use the analysis condition of 20keV, 50nA and 20 μ m defocused beam sizes to analyze lens surface.Beam size is decreased to 5 microns is used for the side analysis.Gate time is 160 seconds at the place, peak, and locating at each non-peak (off-peak) is 80 seconds.
Select the background position to disturb to avoid spectrum.Calculate background intensity by the linear interpolation method between the non-peak position.Also at detector dead time, beam drift and normal intensity drift correction intensity.Any analysis does not all have obviously drift.The detection limit value of Ag is about 40ppm.
Protruding side (antecurvature curved surface) by the oriented side surface and all are crossed all from this point, carry out the side and analyze and obtain the result.Side at the lens materials band begins, with 250 or the 500um step-length stride across whole eyeglass and carry out surface analysis.Total distance is generally 8-12mm (each sample surfaces 25-50 data point).The artificial Z focus of confirming all data points, after guaranteeing waiting for that about 4 hours sample surfaces are stablized about the Z focus, spectrometer does not take place and defocuses in incomplete flat sample.
With the basic standard product of Ag metal as Ag.With standard items and unknown product 20nmSpec-Pure equadag coating, operation under these conditions, but the gate time of standard items is 10 seconds at the place, peak, is 5 seconds at each place, non-peak.
Fig. 1 is at embodiment 16 and the comparing embodiment 1 eyeglass compilation figure that distributes of silver everywhere, wherein form eyeglass after silver be deposited in the eyeglass.Show that as Fig. 1 the metal salt concentrations in embodiment 21 eyeglasses all is consistent (showing by connecting foursquare line) at whole eyeglass everywhere.For the eyeglass of comparing embodiment 2, the eyeglass that Fig. 1 goes back display analysis has high concentration silver in the preceding and rear surface 20% of eyeglass, but silver-colored considerably less (line that connects as rhombus shows) at center.
Embodiment 19
Assess the silver that discharges from eyeglass according in the eyeglass of embodiment 16 preparations in order to following method.
Blot eyeglass to be measured to remove excess liq with sterile gauze (guaze), be transferred in the aseptic 24 porocyte culture plates with 1 eyeglass/hole then, 1ml TLF respectively is housed in the hole.Cover each plate and avoid evaporating and dewater,, stir with 100rpm at least simultaneously 35 ℃ of cultivations.Eyeglass was transferred in the fresh 1ml volume TLF in per 24 hours.In each time interval of measuring, in the hole, take out at least 3 eyeglasses, with 100ml PBS rinsing 3-5 time.On paper handkerchief, blot eyeglass to remove excess liq, be transferred in the propylene scintillation vial (1 eyeglass/bottle).Analyze silver content with neutron activation analysis.
The eyeglass of test comparing embodiment 2 is also as above described.The result of two kinds of eyeglasses as shown in Table 3.In Fig. 2, the solid line that connects Diamond spot is the result of embodiment 16 eyeglasses, and the dotted line of connection side's form point is the assessment result of comparing embodiment 2 eyeglasses.Fig. 2 clearly illustrates that eyeglass of the present invention is slower and as one man discharge antimicrobial metal than the eyeglass (silver salt is deposited in the eyeglass after wherein forming eyeglass) of embodiment 2 frequently.
Embodiment 20
Antimicrobial efficacy in order to following method assessment embodiment 16 and comparing embodiment 2 eyeglasses.Make pseudomonas aeruginosa (Pseudomonas aeruginosa) culture, ATCC#15442 (American Type Culture Collection, Rockville, MD) grow overnight in the tryptic soy medium.Culture washing 3 (3) in phosphate buffered saline (PBS) (PBS, pH=7.4 ± 0.2) is inferior, the bacterial precipitation thing is suspended among the 10mL 2%TSB-PBS again.The preparation bacterial inoculum is about 1 * 10 to obtain final concentration 8Individual colony-forming units/mL (cfu/mL).Serial dilution is 1 * 10 to obtain inoculum density in 2%TSB-PBS 4Cfu/mL.
Aseptic contact lenses are being changed in 3 times the 30mL phosphate buffered saline (PBS) (PBS, pH=7.4+/-0.2) flushing to remove residual solution.The contact lenses of each flushing are put into the independent instrument connection of sterile tissue culture plate with 500 μ L bacterial inoculums, make about 20 hours of the rotation ℃ in oscillator-incubator (100rpm) of this plate then in 35+/-2.Take out each eyeglass of vial, in changing 3 (3) inferior PBS, wash 5 (5) inferior, to remove the cell of loose combination.After the cultivation, take out 3 initial antibiotic effects of eyeglass lens measurement (hereinafter describing) of various type of lenses, the residue eyeglass is transferred to as above to describe is equipped with in each hole of new microtiter plate of 500 μ L TLF.
Residue eyeglass and 1ml TLF/ eyeglass were cultivated 7 and 14 days in tissue culture hole separately, eyeglass was transferred in the fresh TLF solution in per 24 hours.
When culture period finishes (after the cultivation, 7 and 14 days), take out the eyeglass to be measured in each hole, it is inferior to remove the cell of loose combination to change 3 PBS flushings 5 (5), puts into about 10mL and contains 0.05% (w/v) Tween TMIn 80 the PBS,, make the adhesion fracture of remaining bacteria and eyeglass with centrifugal force with 2000rpm vortex 3 minutes.With the bacterium alive of RBD 3000 flow cytometers counting gained supernatant, that the Bacteria Detection result alive who is attached to 3 eyeglasses is average.Result such as Fig. 3 show.Use available from Vistakon's
Figure A20078004897700451
ADVANCE TM, trade mark is Hydraclear TMContact lenses in contrast.
Result such as Fig. 3 of embodiment 16 and comparing embodiment 2 eyeglasses show.The solid line that connects Diamond spot is the result of embodiment 16 eyeglasses, and the dotted line of connection side's form point is the assessment result of comparing embodiment 2 eyeglasses.Fig. 3 showed eyeglass of the present invention through 14 days, and bacterium (pseudomonas aeruginosa (Pseudomonas aeruginosa)) shows the minimizing of consistent 4log.Different with eyeglass of the present invention, the eyeglass of comparing embodiment 2 showed the minimizing of 3log at preceding 7 days, reduce in the remaining assessment phase then, was the minimizing of about 1log at the 14th day.Therefore, the effect of eyeglass performance of the present invention is bigger and more lasting than embodiment 2 eyeglasses frequently.
Embodiment 21
In the agitating solution of 45.5kg 3-allyloxy-2-hydroxy propyl methacrylate (AHM) and 3.4g Butylated Hydroxytoluene (BHT), add 10ml Pt (0) divinyl tetramethyl disiloxane/xylene solution (2.25%Pt concentration), then add 44.9kg normal-butyl poly dimethyl silane.The control exothermic heat of reaction is about 20 ℃ to keep reaction temperature.Behind the full consumption normal-butyl poly dimethyl silane, add 6.9g diethyl ethylenediamine deactivation Pt catalyzer.Extract crude product mixture several times until residual AHM content＜0.1% of residual solution with 181kg ethylene glycol.10g BHT is added gained residual solution and stirring,, then remove residual ethylene glycol, obtain 64.5kg OH-mPDMS until dissolving.6.45g 4-metoxyphenol (MeHQ) is added in the gained liquid, stir and filter, obtain the whole OH-mPDMS of 64.39kg, be colorless oil.
Synthetic embodiment 2: macromonomer preparation
Under environmental temperature and nitrogen, add 30.0g (0.277mol) two (dimethylamino) methyl-monosilane, 13.75mL 1M TBACB solution (386.0g TBACB is in the anhydrous THF of 1000mL), 61.39g (0.578mol) paraxylene, 154.28g (1.541mol) methyl methacrylate (is 1.4 equivalents with respect to initator), 1892.13 (9.352mol) 2-(trimethylsiloxy) ethyl-methyl acrylate (is 8.5 equivalents with respect to initator) and 4399.78g (61.01mol) THF in the drying receptacle in being contained in drying box.The above mixture for preparing in the drying box is packed in the drying that is equipped with the thermocouple that all connects nitrogenous sources and condenser, 3 necks, the round-bottomed flask.
Make reactant mixture be cooled to 15 ℃, stir simultaneously and purge with nitrogen.After solution reaches 15 ℃, in 191.75g (1.100mol) 1-trimethylsiloxy-1-methoxyl group-2-metering system (1 equivalent) injecting reactor.Allow the reactant heat release to about 62 ℃, then the 0.40M solution of 30mL154.4g TBACB in the anhydrous THF of 11mL is metered in the reaction residual.After reaction temperature reaches 30 ℃ and metering beginning, add the solution of 467.56g (2.311mol) 2-(trimethylsiloxy) ethyl-methyl acrylate (is 2.1 equivalents with respect to initator), 3812g (3.63mol) normal-butyl monomethyl acryloxy propyl group-dimethyl silicone polymer (is 3.3 equivalents with respect to initator), 3673.84g (8.689mol), TRIS (is 7.9 equivalents with respect to initator) and 20.0g pair (dimethylamino) methyl-monosilanes.
Allow the mixture heat release to about 38-42 ℃, allow it be cooled to 30 ℃ then.At this moment, the solution that adds 10.0g (0.076mol) two (dimethylamino) methyl-monosilane, 154.26g (1.541mol) methyl methacrylate (is 1.4 equivalents with respect to initator) and 1892.13g (9.352mol) 2-(trimethylsiloxy) ethyl-methyl acrylate (is 8.5 equivalents with respect to initator) allows the mixture heat release to about 40 ℃ once more.Reaction temperature drops to about 30 ℃, adds 2 gallons of THF to reduce viscosity.The solution that adds 439.69g water, 740.6g methyl alcohol and 8.8g (0.068mol) dichloroacetic acid makes mixture reflux 4.5 hours to remove the blocking group on the HEMA.Remove volatile matter then, add toluene and help to remove water until the steam temperature that reaches 110 ℃.
Make reaction flask maintain about 110 ℃, add the solution of 443g (2.201mol) TMI and bismuth K-KAT 348 (5.94g).Make the mixture reaction show that until IR isocyanate peak disappears.The toluene reduction vaporization is obtained canescence, anhydrous, wax shape activated monomer.Macromonomer is put into acetone, and the weight ratio of acetone and macromonomer is about 2: 1.After 24 hours, add entry and make the macromonomer precipitation, macromonomer is filtered, used 45-60 ℃ of vacuum drying oven dry 20-30 hour.
Synthetic embodiment 3: form the AgI Nanodispersion
Following formation metal agent and salt precursor solution: make 10 while stirring, 000ppm AgNO 3Be dissolved in the 50w/w% solution 200gm of PVP K12 in DI water.Make while stirring NaI (10,000ppm) be dissolved in the 50w/w% solution 200gm of PVP K12 in DI water.Under with the 2013rpm condition of stirring, will contain AgNO 3Metal salt solution add in the salt precursor solution with 200gm/ hour speed.It is air-dry that metal salt solution is sprayed.Inlet temperature is 185 ℃, and outlet temperature is 90 ℃, and feed rate is 2.7kg/hr.The water content of stable AgI nanoparticle is less than 5 weight %.
Stable AgI nanoparticle powder (0.32 gram) is dissolved in the 199.7 gram DI water prepares solution.It is the silver of 6600ppm that AgI nanoparticle powder comprises the nominal concentration that is the silver iodide form.The silver concentration that calculates in the whole solution is 11ppm.
Embodiment 22
The method of US 2005/0013842A1 embodiment 10 is below described.
Make silver nitrate (0.127 gram) be dissolved in preparation 0.01M AgNO in the 75ml DI water 3Solution.Make polyacrylic acid (PAA, 2 grams) be dissolved in preparation 4%w/w PAA solution in the 48mL DI water.In 200ml DI water, add sodium borohydride (0.008 gram) preparation 1mM solution.1mM sodium borohydride solution (197mL) is placed in the beaker that is equipped with stirring rod.Beaker is immersed in the ice-water bath.This device is placed on the agitating plate.0.01M liquor argenti nitratis ophthalmicus (2mL) is mixed with 4%w/w PAA solution (1mL), cool off with ice-water bath.Under the condition of stirring silver nitrate-PAA solution mixture is being added in the cold 1mM sodium borohydride solution rapidly fast.Can observe brown-yellow variable color immediately behind the mixed solution.Solution was mixed 8 hours, be transferred to amber jar of interior storage of cleaning then.According to the silver nitrate amount that adds, the silver concentration that calculates whole solution is 11ppm.
Measure the UV-Vis spectrum that present embodiment 22 contains Ag solution, be shown in Fig. 4, and the UV-Vis spectrum of the moisture AgI/PVP solution of synthetic embodiment 3 preparations.Show that as Fig. 4 the broad peak of the spectrum of present embodiment 22 solution concentrates on about 420nm.On the contrary, the main peak of synthetic embodiment 3 moisture AgI/PVP dispersion UV-Vis spectrums concentrates on 330nm.According to Zang, Z. etc., this peak may come from the silver (Ag that exists with ionic species +) and the interaction of PVP in the aqueous solution.Silver in the Discrepancy Description of Fig. 4 spectrum active mixture of the present invention and the Ophthalmoligic instrument may exist with ionic species, but silver-colored in Ag in the active mixture of embodiment 23A, B and E 0Exist.
Embodiment 23A-B (comparison)
The amount that the monomer component (except light trigger Darocur 1173) that table 9 is listed is listed with table 9 is admixed in the amber glass bottle, goes up the blending of rolling at jar roller (jar roller).
In embodiment 23A, (make 0.025gm AgNO available from Fisher with liquor argenti nitratis ophthalmicus 3, the A.C.S. level is dissolved in the 54mL absolute ethyl alcohol available from Fisher) and as the silver nitrate source.In embodiment 23B, (make 0.305gm AgNO available from Fisher with liquor argenti nitratis ophthalmicus 3, the A.C.S. level is dissolved in the 54mL absolute ethyl alcohol available from Fisher) and as the silver nitrate source.
Table 9
Compound 23A ％w/w 23B ％w/w 23C ％w/w 23D ％w/w 23E ％w/w 23F％ w/w
Macromonomer 37.4 37.4 37.4 37.4 37.4 37.4
TRIS 15 15 15 15 15 15
DMA 22.5 22.5 22.5 22.5 22.5 22.5
Darocur 1173 0.3 0.3 0.3 0.3 0.3 0.3
Ethanol 24.8 24.8 24.3 18.9 24.8 24.8
PAA 0 0 0 0 0.022 0
AgNO3 0.005 0.061 0 0 0.052 0
The AgI/K12 powder * 0 0 0.5 5.9 0 0
Ag(ppm) 35 343 37 241 449 0
*Form as synthetic embodiment 3
Allow each 5mL active mixture of 23A and 23B leave standstill 24 hours.Use above-described L *a *b *The color of grade and method quantitative measurment active mixture.The color of subjective evaluation active mixture under white fluorescent also.The result is disclosed in following table 10.
Measure the UV-VIS spectrum of embodiment 23A and B active mixture, be shown in Fig. 5.
Add light trigger (Darocur 1173), make each preparation degassing 5-7 minute in the 660-mmHg vacuum.Then preparation is transferred in the nitrogen protection case.Prepare contact lenses with flexure plane behind antecurvature curved surface of Zeonor and the polypropylene, the deoxidation at least 24 hours in the nitrogen protection case of described flexure plane.Each lens cavities is used 100 μ L dosage, and the frame of fixing len mould is placed under the quartz plate.Eyeglass was solidified 60 minutes under UV irradiation (four parallel Philips TL09/20) lamp.
After the curing, strike the sheet mould of starting shooting with the hand, the taking-up eyeglass is placed on and contains 70: 30 IPA: in the jar of DI aqueous mixtures, and every eyeglass use～5mL solution.After at least 60 minutes, take out the eyeglass mould with tweezers, decanted solution is with 70: 30 fresh IPA: DI aqueous mixtures this jar of packing into.Eyeglass is rolled on the jar roller, and decanted solution after at least 60 minutes is with fresh DI water this jar of packing into.Eyeglass was rolled 60 minutes on the jar roller more at least, and decanted solution is with fresh DI water this jar of packing into.Eyeglass pack with 5mL phosphate-buffered packaging solution in vial, sealed, 122 ℃ of autoclavings 30 minutes with silicone plug and aluminium roll-top.Silver content with INAA measurement eyeglass the results are shown in table 9.
Embodiment 23C and D
Repeat embodiment 23A and B, but add the stable AgI/PVP powder replacement silver nitrate/ethanolic solution of synthetic embodiment 3 preparations.Measure the color of solution according to the description of embodiment 23A and B, the results are shown in table 10.Measure the UV-VIS spectrum of embodiment 23C and D active mixture, the results are shown in Fig. 5.Description according to embodiment 23A and B prepares eyeglass, and the SSPS that contains the 50ppm methylcellulose with 5mL in vial packs, with silicone plug and the sealing of aluminium roll-top, and 122 ℃ of autoclavings 30 minutes.Silver content with INAA measurement eyeglass the results are shown in table 9.
Embodiment 23E
Repeat embodiment 23A, but silver-colored source is 0.026gm silver nitrate and the 0.011PAA that is dissolved in 11.25gm DMA, rather than silver nitrate/ethanolic solution.Measure the color of solution according to the description of embodiment 23A and B, the results are shown in table 10.Measure the UV-VIS spectrum of embodiment 23E active mixture, the results are shown in Fig. 5.Description according to embodiment 23A and B prepares eyeglass.Silver content with INAA measurement eyeglass the results are shown in table 9.
Embodiment 23F
Repeat embodiment 23A, but do not add silver.
Table 10
Embodiment number L ＊ a ＊ b ＊ Visual appearance (color)
23A 85.08 -0.45 2.58 Brown-yellow
23B 73.69 -2.69 8.10 Crineous-yellow
23C 89.40 -1.91 2.77 Light yellow
23D 86.28 -3.84 10.85 Yellow
23E 74.36 -0.67 3.82 Burgundy-yellow
23F 89.67 -1.21 0.96 Colourless
Fig. 5 has compared the UV-Vis spectrum of embodiment 23A-F active mixture.Embodiment 23F (the not control formulation of argentiferous) does not show any peak in the zone that marks.The active mixture that silver concentration is low (embodiment 23A) does not show any peak clearly yet.But embodiment 23B shows tangible peak at 435nm, confirms Ag according to US 2005/0013842 0Existence.
Visible significantly transition (at the 417nm of UV-Vis spectrum) in the spectrum of embodiment 23C.This transition shows and is present in the spectrum of embodiment 23D active mixture (the target silver concentration is about 389ppm), but signal has noise, near composing the saturated of district.Zhang; Z.; Zhao; B.; and Hu; L.; Journal of Solid State Chemistry January 1996; 121; Issue 1; 5,105-110.PVP Protective Mechanism of Ultrafine Silver PowderSynthesized by Chemical Reduction Processes (by the PVP defense mechanism of the synthetic super fine silver powder of chemical reduction method) obtains the curve of spectrum closely similar with sample 23C (when they analyze the UV-Vis spectrum of AgI colloid), absorbs shoulder at 420nm.And they find with sodium borohydride the AgI colloid to be reduced to Ag 0After, the UV-Vis spectrum finding of the position at peak and shape and sample 23B is closely similar.According to the data of scientific literature, to compare with the nitric acid money base monomer of embodiment 23B, there are the silver-colored particulate of the different states of oxidation in the difformity at embodiment 23C peak and position indicating.
Embodiment 24A-F
The effect of the anti-staphylococcus aureus of eyeglass (staphylococcus aureus) 031 that the program test embodiment 23A-F that describes with Test Methods section above forms.The results are shown in following table 11.
Table 11.
The eyeglass of embodiment number Log 10Colony-forming units/eyeglass or mL (cfu/ eyeglass or mL) The standard deviation of cfu/ eyeglass or mL The minimizing % that compares with 23E (contrast) The Log that compares with 23E (contrast) reduces
23F 5.11 0.12 Inapplicable Inapplicable
23A 5.92 0.22 0.0 0.0
23B 5.87 0.11 0.0 0.0
23C 3.07 0.04 99.1 2.0
23D 3.26 0.03 98.6 1.9
23E 4.95 1.07 0.0 0.2
The eyeglass silver concentration of embodiment 23A and B is similar to the eyeglass of embodiment 23C and D respectively.But the antimicrobial acivity data show is compared with the control lenses of embodiment 23F preparation, does not show antimicrobial acivity with the eyeglass (23A, B and E) that contains the preparation of silver nitrate monomer.On the contrary, compare with control lenses according to the eyeglass of the metalline nanoparticle of embodiment 23C and D preparation and show the minimizing of 1log at least.
Embodiment 25A
Repeat embodiment 23D, but, eyeglass was solidified 30 minutes under radiation of visible light (four parallel Philips TL03/20) lamp with visible light light trigger CGI 819.To solidify eyeglass taking-up, extraction, hydration, packing and autoclaving, as be disclosed in embodiment 23D.Measure silver concentration, iodide concentration and colour, the results are shown in following table 12.Also measure silver concentration, iodide concentration and the colour of embodiment 23D eyeglass (solidifying the same preparation of preparation with UV), the results are shown in following table 12 and 13.
Embodiment 25B
Repeat embodiment 25A, but before solidifying, 2wt%Norbloc is added in the preparation, make concentration of alcohol reduce by 2%.Measure silver concentration, iodide concentration and colour in hydration and sterilization back, the results are shown in following table 12 and 13.
Table 12.
Embodiment number On average [Ag] (ppm) Standard deviation [Ag] (ppm) On average [I] (ppm) Standard deviation [I] (ppm) Ag: I mol ratio
25A 485 15 587 18 1.00
25B 471 4 564 6 0.98
25D 241 30 160 52 1.8
As seen according to the silver of embodiment 23D with the eyeglass of ultraviolet light polymerization preparation: iodide mol ratio (measuring in hydration and sterilization back) is approximately 2.This Notes of Key Data only about half of silver content of eyeglass when solidifying is converted into the silver of the different states of oxidation from silver iodide.Believe at embodiment 23D medium ultraviolet light AgI is converted into Ag 0And I 2Because I 2Dissolve in IPA, so when hydration, remove.According to the silver iodide that add active mixture, silver in the expection eyeglass: the iodide mol ratio is approximately 1.
At embodiment 25A and the B silver with the eyeglass of visible-light curing preparation: the iodide mol ratio is approximately 1.Therefore, use the condition of cure outside the UV scope extremely important to keeping antimicrobial metal salt such as silver iodide to be in its salt form.
Table 13.
Embodiment number L ＊ a ＊ b ＊
25A 90.37 -1.39 2.89
25B 89.70 -1.59 3.35
23D 85.53 -3.64 25.77
According to the colorimetric data of table 13, with the eyeglass (embodiment 25A and B) of the comparativity silver concentration of visible-light curing preparation than with obvious more shallow yellow (the lower b of the eyeglass performance of the embodiment 23D of ultraviolet light polymerization preparation *Value).
Embodiment 26-28
Preparation PVP K12 in DI water 100,000ppm solution.This solution (solution A) is used to prepare NaI and AgNO 3Solution.The NaI and the AgNO that prepare about 1500ppm, 5000ppm and 10000ppm respectively 3Solution.Stir various solution until the particulate that is invisible to the naked eye.20mL NaI solution is placed in the clean jar, place magnetic stirrer in it.Agitator is set at 300rpm, with 20ml AgNO 3In the speed adding NaI solution that hereinafter table 14 shows.Carry out all mixing at ambient temperature.The turbidity of subjective evaluation solution the results are shown in following table 14 when the listed interpolation time finishes.The various concentration and the interpolation speed that show with table 14 repeat embodiment.
Table 14
Add speed (ml/sec) The interpolation time (sec) Embodiment 26 1500ppm Embodiment 27 5000ppm Embodiment 28 10,000ppm
20 1 Transparent Emulsus Emulsus
4 5 Transparent Slight muddy Emulsus
2 10 Transparent Transparent Slight muddy
1 20 Transparent Transparent Transparent
0.67 30 Transparent Transparent Transparent
Embodiment 29-31
Repeat embodiment 26-28, but NaI solution is added AgNO 3In the solution.The results are shown in following table 15.
Table 15
Add speed (ml/sec) The interpolation time (sec) Embodiment 29 1500ppm Embodiment 30 5000ppm Embodiment 31 10,000ppm
20 1 Transparent Emulsus Emulsus
4 5 Transparent Emulsus Emulsus
2 10 Transparent Emulsus Emulsus
1 20 Transparent Emulsus Slight muddy
0.67 30 Transparent Transparent Transparent
Embodiment 32
Repeat embodiment 31, but metal agent and salt precursor solution were mixed on the jar roller～5 days approximately, then with the various solution batch mixed of 20ml (being poured on together in about 1 second).The result is the clear solution that contains the PVP-AgI complex compound.
Embodiment 33-39
At the PVP concentration PVPK12 of (1% to 35%PVP K12 is in DI water) as shown in Table 16: form about 10mL 700ppm AgNO in the DI aqueous solution 3Solution.With every kind of AgNO 3Drips of solution adds in the 10mL 1100ppm NaI/DI solution (no PVP), vibrates to form dispersion with hand.Embodiment 33 is an emulsus, and all the other embodiment are adding AgNO 3The time remain transparent.Measure the granularity of gained AgI dispersion with laser scattering method (embodiment 33) and photon correlation spectroscopy method (embodiment 35-39).Data are represented with the z-mean of size distribution.
Table 16
Embodiment number [PVP K12](wt％) Granularity (nm)
33 0％ 10600
34 1％ 270
35 2％ 40
36 10％ 540
37 15％ 400
38 25％ 40
39 35％ 20
The data of table 16 are shown in Fig. 5 with chart.The data of table 16 clearly illustrate that the existence of PVP when forming slaine obviously reduces granularity (at least 2 orders of magnitude).
Embodiment 40-44
Repeat embodiment 34, but replace PVP with the listed dispersant of the table 17 of the listed concentration of table 17.Measure the granularity of gained AgI dispersion with laser scattering method (40,41 and 43) and photon correlation spectroscopy method (42,44).Data are represented with the z-mean of size distribution.
Table 17
Embodiment number Dispersant Granularity (nm)
40 5％PAA 2K 2760
41 5％PEO 10K 7020
42 10％PEO 10K 475
43 Glycerine 6380
44 PVA 120K 470
Embodiment 45
The amount that the component that following table 18 is shown is listed with table 18 is admixed together in the amber glass bottle, rolls on the jar roller.Mixture is dispensed in the contact lenses mould (Zeonor front and rear curved face mould tool), solidifies under the following conditions: 2.8+/-0.5%O 2Visible-light curing (PhilipsTL03 lamp); Intensity distributions: 25 ℃ of 1+/-0.5mW/cm 2(10-60sec), 80+/-5 ℃ 5.5+/-0.5mW/cm 2(304-600sec).Make eyeglass hydration in the IPA/ aqueous mixtures, 950 microlitres that are packaged in the independent polypropylene blister package contain in the SSPS of 50ppm methylcellulose, 124 ℃ of autoclavings 18 minutes.
Figure A20078004897700551
The effect of 12 anti-staphylococcus aureuses of eyeglass (staphylococcus aureus) 031 that the program test present embodiment of describing with Test Methods section above 45 forms.The control lenses that does not comprise the silver iodide nanoparticle with the method preparation of embodiment 45.The log reduction (compared with the control) of measuring the argentiferous eyeglass is 3.3 ± 02 (mean+/-standard deviation).
Embodiment 46
In the clinical testing of the double blinding of using embodiment 45 control lenses, offside, allow 30 patients (all being present recessive glasse wearer) wear the eyeglass of embodiment 45.Patient wear eyeglass 14 days, wear every day, uses OptiFree RepleniSH, instructs the patient at eyeglass its eyeglass that cleans and rub during sterilization.The eyeglass of embodiment 45 comprises about 10 μ g silver when baseline.
The phase of wearing at 14 days is collected the eyeglass of 26 patient wears finishing research when finishing, test silver content with INAA.Average rate of release with INAA data computation silver is μ g every day 0.5.Also use the above activity of the anti-staphylococcus aureus of method testing lens (S.aureus) of Test Methods section description.The log reduction (with wearing contrast and comparing) of measuring embodiment 45 eyeglasses is 3.4 ± 1.2 (mean+/-standard deviation).

Claims (39)

1. articles for use that form with at least a polymer, this polymer comprises the antimicrobial metal salt particulate of equally distributed granularity less than about 200nm, wherein said articles for use make pseudomonas aeruginosa and at least a demonstration of staphylococcus aureus at least about the minimizing of 0.5log, compare at about 70 micron thickness turbidity values less than about 100% with the CSI eyeglass.
2. the articles for use of claim 1, wherein said articles for use are medical treatment devices.
3. the articles for use of claim 1, wherein said articles for use are Ophthalmoligic instruments.
4. the Ophthalmoligic instrument of claim 3, wherein said Ophthalmoligic instrument is worn after date and is comprised at least about 0.5 μ g antimicrobial metal predetermined.
5. the articles for use of claim 1, wherein said antimicrobial metal salt particulate is formula [M Q+] a[X Z-] b, wherein X is any negatively charged ions, and M is any positive charge metal, and a, b, q and z independently be 〉=1 integer, and q (a)=z (b).
6. the articles for use of claim 5, wherein M is selected from Al + 3, Co + 2, Co + 3, Ca + 2, Mg + 2, Ni + 2, Ti + 2, Ti + 3, Ti + 4, V + 2, V + 3, V + 5, Sr + 2, Fe + 2, Fe + 3, Au + 2, Au + 3, Au + 1, Ag + 2, Ag + 1, Pd + 2, Pd + 4, Pt + 2, pt + 4, Cu + 1, Cu + 2, Mn + 2, Mn + 3, Mn + 4, Se + 4And Zn + 2
7. the articles for use of claim 1, wherein M is selected from Mg + 2, Zn + 2, Cu + 1, Cu + 2, Au + 2, Au + 3, Au + 1, Pd + 2, Pd + 4, Pt + 2, Pt + 4, Ag + 2And Ag + 1
8. the articles for use of claim 5, wherein M comprises Ag + 1
9. the articles for use of claim 5, wherein X is selected from and comprises CO 3 -2, SO 4 -2, PO 4 -3, Cl -1, I -1, Br -1, S -2, O -2Ion with acetate.
10. the articles for use of claim 5, wherein X is selected from CO 3 -2, SO 4 -2, Cl -1, I -1, Br -1And acetate.
11. the articles for use of claim 1, wherein the slaine particulate is selected from the particulate of silver carbonate, silver orthophosphate, silver sulfide, silver chlorate, silver bromide, silver iodide and silver oxide.
12. the articles for use of claim 1, wherein the slaine particulate comprises at least a salt, and described salt is selected from manganese sulfide, zinc oxide, zinc carbonate, calcium sulphate, selenium sulfide, cupric iodide, copper sulfide and cupric phosphate.
13. the articles for use of claim 5, when wherein measuring in about 25 ℃ of pure water, the solubility product constant of slaine is 2 * 10 -10Or it is littler.
14. the articles for use of claim 1, the granularity of wherein said slaine particulate is less than about 100nm.
15. the articles for use of claim 1, wherein based on the dry weight basis of described articles for use, described polymer comprises about 0.1ppm to about 10 weight % metals.
16. the articles for use of claim 1, wherein based on the dry weight basis of described articles for use, described polymer comprises about 1ppm to about 1 weight % metal.
17. the articles for use of claim 1, wherein said polymer is a hydrogel.
18. the articles for use of claim 1, wherein said articles for use also comprise the b less than about 4 *Value and at least about 89 L *Value, genetic system.
19. the articles for use of claim 1, wherein said polymer also comprise at least a UV absorption compound.
20. the articles for use of claim 1, the amount that wherein said at least a UV absorption compound exists are enough to blocking-up and pass described device at least about 90% ultraviolet light.
21. method that comprises the following steps
(a) make at least a salt precursor, optional and at least a living polymer component of mixture is dissolved in the solvent to form the salt precursor mixture;
(b) make at least a metal agent and at least a dispersant, optional and at least a active component are dissolved in and form dispersant-metal agent complex compound in the solvent, and to form the metal agent mixture, wherein said solvent and component can be identical or different;
(c) mix described salt precursor mixture and described metal agent mixture under the particulate formation condition, contain particle mixture with formation, described mixture comprises at least a antimicrobial metal salt [M Q+] a[X Z-] b;
(d) make other active component and described containing optional mixing of particle mixture contain the particulate active mixture with formation; Prerequisite is when when step (a) and (b) not comprising active component, then to add at least a active component in step (d); With
(e) make and describedly contain particulate active mixture reaction forming antimicrobial polymeric articles, what described reaction condition was enough to make described metal agent that step (c) adds remains M at least about 90%M in described polymeric articles Q+
22. the method for claim 21 wherein optionally is used for step (a) or (b) at least a active component and metal agent are reactionless.
23. the method for claim 21 wherein in blend step (d), will contain in the particulate active mixture with the adding of metal agent reactive activity component.
24. the method for claim 21, wherein said dispersant are selected from borate of hydroxyalkyl methyl cellulose polymer, polyvinyl alcohol, polyvinylpyrrolidone, PEO, starch, pectin, polyacrylamide, gelatin, polyacrylic acid, organoalkoxysilane 3-aminopropyltriethoxywerene werene, MTES, phenyltrimethoxysila,e, VTES and 3-glycidoxypropyltrimewasxysilane, glycerine and composition thereof.
25. the method for claim 21, wherein said dispersant is selected from borate of hydroxyalkyl methyl cellulose polymer, polyvinyl alcohol, polyvinylpyrrolidone, PEO, gelatin and polyacrylic acid, glycerine and composition thereof.
26. the method for claim 21, wherein said dispersant is selected from HYDROXY PROPYL METHYLCELLULOSE, polyvinyl alcohol, polyvinylpyrrolidone, PEO, gelatin and polyacrylic acid and composition thereof.
27. the method for claim 21, wherein said dispersant is selected from polyvinyl alcohol, polyvinylpyrrolidone, PEO and polyacrylic acid and composition thereof.
28. the method for claim 27, the molecular weight of wherein said dispersant is less than about 2,000,000.
29. the method for claim 27, the molecular weight of wherein said dispersant are about 20,000-about 1,500,000.
30. the method for claim 21, wherein said metal agent mixture comprise about at the most 40 weight % dispersants.
31. the method for claim 21, wherein said metal agent mixture comprise the about 30 weight % dispersants of 0.01 weight %-.
32. the method for claim 21, wherein said salt precursor mixture comprise about at the most 10 weight % salt precursors.
33. the method for claim 21, wherein said metal salt precursor mixture comprises the salt precursor with respect to described metal agent molar excess.
34. the method for claim 21, wherein said metal agent mixture comprise about at the most 10 weight % metal agents.
35. the method for claim 21 is wherein removed the described solvent that contains particle mixture before in step (d).
36. method that comprises the curing activity mixture, it is about 200nm or littler stable antimicrobial metal salt particulate and at least a free radical activity component that described mixture comprises granularity, described method is used light, heat or its combination of wavelength above the correction critical wavelength of described slaine particulate, contains the articles for use of antimicrobial metal salt particulate with formation.
37. the method for claim 36, wherein said stable antimicrobial metal salt particulate comprises at least a silver metal salt, and described correction critical wavelength is about 430mn.
38. the method for claim 36, wherein said antimicrobial metal has formula [M Q+] a[X Z-] b, be M at least about 90%M in the described polymer Q+
39. the method for claim 36, wherein said active mixture also comprise at least a UV absorption compound.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107596437A (en) * 2017-10-24 2018-01-19 无锡微色谱生物科技有限公司 A kind of method for the aerogel dressing for preparing the particle containing nano silver/silver chloride
US9953741B2 (en) 2013-01-22 2018-04-24 Bs Support Co., Ltd. Plastic molded product comprising copper-based compound microparticles and preparation method therefor
CN113181431A (en) * 2021-03-16 2021-07-30 浙江大学 Antibacterial and osteointegrative coating formed on surface of substrate and method for preparing antibacterial and osteointegrative coating on surface of substrate
CN116671516A (en) * 2023-08-04 2023-09-01 云南熙乐科技有限公司 Preparation method of aqueous self-degradation antibacterial spray

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6177550A (en) * 1984-09-25 1986-04-21 Mazda Motor Corp Brake system of car
WO2010077985A1 (en) * 2008-12-16 2010-07-08 Board Of Regents, The University Of Texas System In situ formation of nanoparticles in resins
WO2010147779A2 (en) 2009-06-15 2010-12-23 Dsm Ip Assets B.V. Phosphorylcholine-based amphiphilic silicones for medical applications
WO2011032845A2 (en) * 2009-09-15 2011-03-24 Basf Se Aqueous dispersions containing antimicrobials in a hybrid network
CA2787888C (en) 2010-02-16 2016-04-19 Toray Industries, Inc. Low water content soft lens for eye, and method for producing the same
JP5837288B2 (en) * 2010-07-15 2015-12-24 株式会社Ｎｂｃメッシュテック Antiviral agent
AU2012258633A1 (en) * 2011-05-24 2013-11-28 Agienic, Inc. Compositions and methods for antimicrobial metal nanoparticles
US9155310B2 (en) * 2011-05-24 2015-10-13 Agienic, Inc. Antimicrobial compositions for use in products for petroleum extraction, personal care, wound care and other applications
RU2473216C1 (en) * 2011-05-27 2013-01-27 Владимир Игоревич Мащенко Method of obtaining modelling mass for with biocidal properties
US8634068B2 (en) * 2011-06-16 2014-01-21 Johnson & Johnson Vision Care, Inc. Method of determining the optimal wavelength for inspecting ophthalmic lenses
CA2840611A1 (en) 2011-06-30 2013-01-03 Dsm Ip Assets B.V. Silicone-containing monomer
JP6070193B2 (en) 2011-08-17 2017-02-01 東レ株式会社 Medical device and manufacturing method thereof
WO2013024856A1 (en) 2011-08-17 2013-02-21 東レ株式会社 Medical device, and method for producing same
KR101900993B1 (en) 2011-08-17 2018-09-20 도레이 카부시키가이샤 Medical treatment device, composition for coating solution, and method for manufacturing medical treatment device
US20130323295A1 (en) * 2011-12-08 2013-12-05 Johnson & Johnson Vision Care, Inc. Monomer systems with dispersed silicone-based engineered particles
GB201201508D0 (en) * 2012-01-30 2012-03-14 Harman Technology Ltd Silver halide compositions
JP2013209338A (en) * 2012-03-30 2013-10-10 Nbc Meshtec Inc Bactericide
EP2900409B1 (en) 2012-09-27 2019-05-22 Rhodia Operations Process for making silver nanostructures and copolymer useful in such process
US11352551B2 (en) 2012-11-26 2022-06-07 Agienic, Inc. Proppant coatings containing antimicrobial agents
US10208241B2 (en) 2012-11-26 2019-02-19 Agienic, Inc. Resin coated proppants with antimicrobial additives
KR101406779B1 (en) * 2013-01-22 2014-06-17 (주)비에스써포트 Thermoplastic resin fiber having nano particle of conductive copper compound and method of manufacturing the fiber
GB2511528A (en) 2013-03-06 2014-09-10 Speciality Fibres And Materials Ltd Absorbent materials
KR101602659B1 (en) * 2013-07-09 2016-03-11 (주)비에스써포트 Thermoplastic resin wares having fine particle of copper compound and method of manufacturing the same
US11052177B2 (en) * 2013-09-06 2021-07-06 The Trustees Of The University Of Pennsylvania Antimicrobial polymer layers
RU2550398C1 (en) * 2013-11-12 2015-05-10 Федеральное государственное бюджетное учреждение науки Институт химиии твердого тела и механохимии Сибирского отделения Российской академии наук (ИХТТМ СО РАН) Antimicrobial filter material and method for producing it
DE102013112404B4 (en) 2013-11-12 2023-03-16 ACTEGA Schmid Rhyner AG Production of polymer particles and rough coatings using ink-jet printing
KR101621242B1 (en) 2014-03-17 2016-05-16 (주)비에스써포트 Medical tubes having copper based compound
KR101564328B1 (en) * 2014-04-28 2015-10-29 (주)비에스써포트 Plastic deposited with copper based compound and method of manufacturing the plastic
KR101625906B1 (en) * 2014-04-28 2016-05-31 (주)비에스써포트 Artificial biomaterial using copper based compound
US10138038B2 (en) 2014-06-05 2018-11-27 Thomas & Betts International, Llc Antimicrobial detectable cable tie
KR101647672B1 (en) * 2014-10-30 2016-08-11 (주)비에스써포트 Microporous membrane for filter having of copper based compound
US10518950B2 (en) * 2014-11-06 2019-12-31 Thomas & Betts International Llc Antimicrobial cable tie
US9519219B2 (en) 2015-03-18 2016-12-13 Eastman Kodak Company Silver-containing compositions containing reactive polymers
WO2016154070A1 (en) * 2015-03-20 2016-09-29 William Marsh Rice University Hypothermic 3d bioprinting of living tissues supported by perfusable vasculature
US10745570B2 (en) 2015-05-18 2020-08-18 Eastman Rodack Company Copper-containing articles
US9963614B2 (en) 2015-05-18 2018-05-08 Eastman Kodak Company Copper-containing articles and methods for providing same
EP3133111A1 (en) * 2015-08-21 2017-02-22 Kaunas University of Technology Method for fabrication of silver nanoparticles containing aliphatic silicone acrylate based organic-inorganic composite coating with antibacterial activity
KR101652274B1 (en) * 2015-12-16 2016-08-30 (주)비에스써포트 Artificial biomaterial using copper based compound
RU2621301C1 (en) * 2016-03-24 2017-06-01 Федеральное государственное бюджетное образовательное учреждение высшего образования "Волгоградский государственный технический университет" (ВолгГТУ) Method of obtaining highly-dispersed stabilized particles of sodium iodide in water solutions
CN109312107B (en) * 2016-06-06 2020-10-30 纺织和塑料研究协会图林根研究院 Polyester and polyolefin molding compounds having biologically active properties and molded bodies produced therefrom
US10676575B2 (en) * 2016-10-06 2020-06-09 Johnson & Johnson Vision Care, Inc. Tri-block prepolymers and their use in silicone hydrogels
JP6984122B2 (en) 2016-12-15 2021-12-17 東洋製罐グループホールディングス株式会社 Dispersion with antiviral properties
WO2018187548A2 (en) * 2017-04-05 2018-10-11 Arizona Board Of Regents On Behalf Of Arizona State University Antimicrobial susceptibility testing with large-volume light scattering imaging and deep learning video microscopy
WO2019028222A1 (en) * 2017-08-02 2019-02-07 Multi Radiance Medical System and method for directing light into a patient's eye
US11638833B2 (en) 2017-08-02 2023-05-02 Multi Radiance Medical Reducing light polution in photobiomodulation therapy of a patients eye
US10996491B2 (en) 2018-03-23 2021-05-04 Johnson & Johnson Vision Care, Inc. Ink composition for cosmetic contact lenses
WO2019198896A1 (en) * 2018-04-12 2019-10-17 숙명여자대학교산학협력단 Antibacterial hydrogel for maintaining freshness of food
TW202009019A (en) * 2018-08-28 2020-03-01 優你康光學股份有限公司 A moisturizing composition of a contact lens
KR102159032B1 (en) * 2018-09-12 2020-09-23 (주) 화진산업 A process for the preparing the antibacterial coating film of photo-curing type containing goethite and the antibacterial coating film prepared therefrom
KR102204904B1 (en) * 2018-11-29 2021-01-20 주식회사 그린폴리머 Manufacturing method of antibacterial plastics molded articles for parts of air cleaner
US11378822B2 (en) 2018-12-12 2022-07-05 Verily Life Sciences Llc Electrowetting ophthalmic devices with anion getter
CN109821060B (en) * 2019-01-17 2021-04-30 太原理工大学 Preparation method of hydrogel medical dressing for promoting wound healing
US11891526B2 (en) 2019-09-12 2024-02-06 Johnson & Johnson Vision Care, Inc. Ink composition for cosmetic contact lenses
WO2021127306A1 (en) * 2019-12-18 2021-06-24 Ascend Performance Materials Operations Llc Processes for producing fiber and fabrics with zinc content
EP4087655A4 (en) * 2020-01-10 2024-02-21 Azura Ophthalmics Ltd Instructions for composition and sensitivity

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5196458A (en) * 1991-10-15 1993-03-23 Johnson & Johnson Vision Products, Inc. Soft, high oxygen permeability ophthalmic lens
DE69917285T2 (en) * 1998-08-14 2005-05-19 Coloplast A/S STABILIZED COMPOSITIONS WITH ANTIBACTERIAL EFFICACY
US6716895B1 (en) * 1999-12-15 2004-04-06 C.R. Bard, Inc. Polymer compositions containing colloids of silver salts
US7179849B2 (en) * 1999-12-15 2007-02-20 C. R. Bard, Inc. Antimicrobial compositions containing colloids of oligodynamic metals
US20040151755A1 (en) * 2000-12-21 2004-08-05 Osman Rathore Antimicrobial lenses displaying extended efficacy, processes to prepare them and methods of their use
ES2369640T3 (en) * 2002-05-24 2011-12-02 Angiotech International Ag COMPOSITIONS AND METHODS TO COVER MEDICAL IMPLANTS.
JP2004081295A (en) * 2002-08-23 2004-03-18 Tokyo Electron Ltd Artificial inner ear
US20040150788A1 (en) * 2002-11-22 2004-08-05 Ann-Margret Andersson Antimicrobial lenses, processes to prepare them and methods of their use
WO2004047878A1 (en) * 2002-11-22 2004-06-10 Johnson & Johnson Vision Care, Inc. Antimicrobial lenses displaying extended efficacy
US20040208983A1 (en) * 2003-04-16 2004-10-21 Hill Gregory A. Antimicrobial coatings for ophthalmic devices
US8425926B2 (en) * 2003-07-16 2013-04-23 Yongxing Qiu Antimicrobial medical devices
JP4117231B2 (en) * 2003-08-05 2008-07-16 Ｈｏｙａ株式会社 Plastic lens and manufacturing method thereof
US8900624B2 (en) * 2004-07-30 2014-12-02 Kimberly-Clark Worldwide, Inc. Antimicrobial silver compositions

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9953741B2 (en) 2013-01-22 2018-04-24 Bs Support Co., Ltd. Plastic molded product comprising copper-based compound microparticles and preparation method therefor
US10096397B2 (en) 2013-01-22 2018-10-09 Bs Support Co., Ltd. Plastic molded product comprising copper-based compound microparticles and preparation method therefor
CN107596437A (en) * 2017-10-24 2018-01-19 无锡微色谱生物科技有限公司 A kind of method for the aerogel dressing for preparing the particle containing nano silver/silver chloride
CN113181431A (en) * 2021-03-16 2021-07-30 浙江大学 Antibacterial and osteointegrative coating formed on surface of substrate and method for preparing antibacterial and osteointegrative coating on surface of substrate
CN113181431B (en) * 2021-03-16 2022-06-28 浙江大学 Antibacterial and osseointegrative coating formed on surface of substrate and method for preparing antibacterial and osseointegrative coating on surface of substrate
CN116671516A (en) * 2023-08-04 2023-09-01 云南熙乐科技有限公司 Preparation method of aqueous self-degradation antibacterial spray

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